The Vaginal Community State Types Microbiome-Immune Network as Key Factor for Bacterial Vaginosis and Aerobic Vaginitis

Regarding bacterial vaginosis (BV), the relevance of the vaginal microbiota to the women's health fulfills a key role, but knowledge gaps regarding aerobic vaginitis (AV) exist. This study aims to characterize vaginal microbiome and its relationship with the local immune mediators, providing an opportunity to define the link between vaginal commensal microorganisms and opportunistic pathogens in the relation of a given vaginal community state type (CST). A total of 90 vaginal samples from Caucasian asymptomatic women of reproductive age (18-40 years) attending the yearly examination and not reporting any vaginal complaints were retrospectively evaluated for microbiome assessment and immune factor dosage. The samples were tested by the Ion Torrent PGM and the Luminex Bio-Plex technologies for the analysis of microbiome and immune factors, respectively. In our study, the CST classification together with the local immune response profiling represented a good predictive indicator of the vaginal health, suggesting that the predominance of a specific Lactobacillus and its relative abundance are pivotal elements to maintain a physiologic status. A vaginal colonization from Bifidobacterium may absolve a protective role similar to that of Lactobacillus, corresponding to a newly identified CST, although studies are needed to better clarify its clinical significance. Moreover, within each CST, a different pattern of inflammation is activated and orchestrated both by the dominant Lactobacillus spp. and by specific non-Lactobacillus bacteria and can give insights into the pathogenic mechanisms. In conclusion, this study contributes to the characterization of vaginal dysbiosis, reshaping this concept by taking into consideration the CST profiling, local immune marker, and immune-microbial network

Multiwavelength observation from radio through very-high-energy Gamma-ray of OJ 287 during the 12-year cycle flare in 2007

We performed simultaneous multiwavelength observations of OJ 287 with the Nobeyama Millimeter Array for radio, the KANATA telescope and the KVA telescope for optical, the Suzaku satellite for X-ray and the MAGIC telescope for very high energy (VHE) gamma-ray in 2007. The observations were conducted for a quiescent state in April and in a flaring state in November-December. We clearly observed increase of fluxes from radio to X-ray bands during the flaring state while MAGIC could not detect significant VHE gamma-ray emission from the source. We could derive an upper limit (95% confidence level) of 1.7% of the Crab Nebula flux above 150 GeV from about 41.2 hours of the MAGIC observation. A simple SSC model suggests that the observed flaring activity could be caused by evolutions in the distribution of the electron population rather than changes of the magnetic field strength or Doppler beaming factor in the jet.Comment: Contribution to the 31st ICRC, Lodz, Poland, July 200

Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects

Oncogenic Virome Benefits from the Different Vaginal Microbiome-Immune Axes.

The picture of dynamic interaction between oncogenic viruses and the vaginal bacteria-immune host milieu is incomplete. We evaluated the impact of Polyomaviridae, Papillomaviridae, and Herpesviridae oncoviruses on the vaginal Community State Types (CSTs) and host immune response in reproductive-age women. In our cohort, only Polyomaviridae and Papillomaviridae were detected and were associated with changes in the resident bacteria of CST I and IV (p < 0.05). Lactobacillus crispatus increased in CST I while Prevotella timonensis and Sneathia sanguinegens increased in CST IV. Conversely, CST II and III showed an alteration of the immune response, with the decrease of Eotaxin, MCP-1, IL-7, IL-9, and IL-15 (p < 0.05), leading to reduced antiviral efficacy. An efficient viral clearance was observed only in women from CST I, dominated by Lactobacillus crispatus. Our in vivo study begins to address the knowledge gap with respect to the role of vaginal bacteria and immune response in susceptibility to oncoviral infections

Fungal burden, dimorphic transition and candidalysin: Role in Candida albicans-induced vaginal cell damage and mitochondrial activation in vitro

Candida albicans (C. albicans) can behave as a commensal yeast colonizing the vaginal mucosa, and in this condition is tolerated by the epithelium. When the epithelial tolerance breaks down, due to C. albicans overgrowth and hyphae formation, the generated inflammatory response and cell damage lead to vulvovaginal candidiasis (VVC) symptoms. Here, we focused on the induction of mitochondrial reactive oxygen species (mtROS) in vaginal epithelial cells after C. albicans infection and the involvement of fungal burden, morphogenesis and candidalysin (CL) production in such induction. Bioluminescent (BLI) C. albicans, C. albicans PCA-2 and C. albicans 529L strains were employed in an in vitro infection model including reconstituted vaginal epithelium cells (RVE), produced starting from A-431 cell line. The production of mtROS was kinetically measured by using MitoSOXTM Red probe. The potency of C. albicans to induced cell damage to RVE and C. albicans proliferation have also been evaluated. C. albicans induces a rapid mtROS release from vaginal epithelial cells, in parallel with an increase of the fungal load and hyphal formation. Under the same experimental conditions, the 529L C. albicans strain, known to be defective in CL production, induced a minor mtROS release showing the key role of CL in causing epithelial mithocondrial activation. C. albicans PCA-2, unable to form hyphae, induced comparable but slower mtROS production as compared to BLI C. albicans yeasts. By reducing mtROS through a ROS scavenger, an increased fungal burden was observed during RVE infection but not in fungal cultures grown on abiotic surface. Collectively, we conclude that CL, more than fungal load and hyphae formation, seems to play a key role in the rapid activation of mtROS by epithelial cells and in the induction of cell-damage and that mtROS are key elements in the vaginal epithelial cells response to C. albicans

Steady State Convergence Acceleration of the Generalized Lattice Boltzmann Equation with Forcing Term through Preconditioning

Several applications exist in which lattice Boltzmann methods (LBM) are used to compute stationary states of fluid motions, particularly those driven or modulated by external forces. Standard LBM, being explicit time-marching in nature, requires a long time to attain steady state convergence, particularly at low Mach numbers due to the disparity in characteristic speeds of propagation of different quantities. In this paper, we present a preconditioned generalized lattice Boltzmann equation (GLBE) with forcing term to accelerate steady state convergence to flows driven by external forces. The use of multiple relaxation times in the GLBE allows enhancement of the numerical stability. Particular focus is given in preconditioning external forces, which can be spatially and temporally dependent. In particular, correct forms of moment-projections of source/forcing terms are derived such that they recover preconditioned Navier-Stokes equations with non-uniform external forces. As an illustration, we solve an extended system with a preconditioned lattice kinetic equation for magnetic induction field at low magnetic Prandtl numbers, which imposes Lorentz forces on the flow of conducting fluids. Computational studies, particularly in three-dimensions, for canonical problems show that the number of time steps needed to reach steady state is reduced by orders of magnitude with preconditioning. In addition, the preconditioning approach resulted in significantly improved stability characteristics when compared with the corresponding single relaxation time formulation.Comment: 47 pages, 21 figures, for publication in Journal of Computational Physic