Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs). Material and methods: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children’s faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome. Results: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases. Conclusions: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics

Dynamical response of the "GGG" rotor to test the Equivalence Principle: theory, simulation and experiment. Part I: the normal modes

Recent theoretical work suggests that violation of the Equivalence Principle might be revealed in a measurement of the fractional differential acceleration $\eta$ between two test bodies -of different composition, falling in the gravitational field of a source mass- if the measurement is made to the level of $\eta\simeq 10^{-13}$ or better. This being within the reach of ground based experiments, gives them a new impetus. However, while slowly rotating torsion balances in ground laboratories are close to reaching this level, only an experiment performed in low orbit around the Earth is likely to provide a much better accuracy. We report on the progress made with the "Galileo Galilei on the Ground" (GGG) experiment, which aims to compete with torsion balances using an instrument design also capable of being converted into a much higher sensitivity space test. In the present and following paper (Part I and Part II), we demonstrate that the dynamical response of the GGG differential accelerometer set into supercritical rotation -in particular its normal modes (Part I) and rejection of common mode effects (Part II)- can be predicted by means of a simple but effective model that embodies all the relevant physics. Analytical solutions are obtained under special limits, which provide the theoretical understanding. A simulation environment is set up, obtaining quantitative agreement with the available experimental data on the frequencies of the normal modes, and on the whirling behavior. This is a needed and reliable tool for controlling and separating perturbative effects from the expected signal, as well as for planning the optimization of the apparatus.Comment: Accepted for publication by "Review of Scientific Instruments" on Jan 16, 2006. 16 2-column pages, 9 figure

Immune checkpoint inhibitors in pre-treated gastric cancer patients: Results from a literature-based meta-analysis

Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64\u20131.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy

The chaotic behavior of the black hole system GRS 1915+105

A modified non-linear time series analysis technique, which computes the correlation dimension $D_2$, is used to analyze the X-ray light curves of the black hole system GRS 1915+105 in all twelve temporal classes. For four of these temporal classes $D_2$ saturates to $\approx 4-5$ which indicates that the underlying dynamical mechanism is a low dimensional chaotic system. Of the other eight classes, three show stochastic behavior while five show deviation from randomness. The light curves for four classes which depict chaotic behavior have the smallest ratio of the expected Poisson noise to the variability ($< 0.05$) while those for the three classes which depict stochastic behavior is the highest ($> 0.2$). This suggests that the temporal behavior of the black hole system is governed by a low dimensional chaotic system, whose nature is detectable only when the Poisson fluctuations are much smaller than the variability.Comment: Accepted for publication in Astrophysical Journa

Halitosis Treatment Through the Administrationof Antibiotic-Resistant Probiotic Lactic YeastKluyveromyces Marxianus Fragilis B0399 (K-B0399)

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The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a complex disease trait where genetic variations and environment interact to determine disease progression. The association of PNPLA3 with advanced disease has been consistently demonstrated but many other modifier genes remain unidentified. In NAFLD, increased fatty acid oxidation produces high levels of reactive oxygen species. Manganese-dependent superoxide dismutase (MnSOD), encoded by the SOD2 gene, plays an important role in protecting cells from oxidative stress. A common non-synonymous polymorphism in SOD2 (C47T; rs4880) is associated with decreased MnSOD mitochondrial targeting and activity making it a good candidate modifier of NAFLD severity. METHODS: The relevance of the SOD2 C47T polymorphism to fibrotic NAFLD was assessed by two complementary approaches: we sought preferential transmission of alleles from parents to affected children in 71 family trios and adopted a case-control approach to compare genotype frequencies in a cohort of 502 European NAFLD patients. RESULTS: In the family study, 55 families were informative. The T allele was transmitted on 47/76 (62%) possible occasions whereas the C allele was transmitted on only 29/76 (38%) occasions, p=0.038. In the case control study, the presence of advanced fibrosis (stage>1) increased with the number of T alleles, p=0.008 for trend. Multivariate analysis showed susceptibility to advanced fibrotic disease was determined by SOD2 genotype (OR 1.56 (95% CI 1.09-2.25), p=0.014), PNPLA3 genotype (p=0.041), type 2 diabetes mellitus (p=0.009) and histological severity of NASH (p=2.0×10(-16)). CONCLUSIONS: Carriage of the SOD2 C47T polymorphism is associated with more advanced fibrosis in NASH

The complexity of soil biological sustainability

Additions of organic amendments to soil not only compensate for decreased soil C, but also contribute to energy requirements for conserving biological activity levels. The soil microbial biomass displays some highly conserved, and possibly unique, characteristics that do not permit a classic interpretation of microbial metabolic parameter data. The resilience of soil microbial biomass and the role of soil organic matter in sustaining microbial biomass under practically zero C inputs were assessed in two long term incubation experiments using soils from the Broadbalk experiment at Rothamsted (UK). Soils with low organic C contents, showed the greatest decline in biomass C during the first 30 d of incubation. The ATP concentration of this rapidly declining microbial biomass did not change during the prolonged incubation period, confirming this peculiar character of the soil microbial biomass. Specific respiration rate did not depend upon substrate availability, being higher in soils that had received the lowest C inputs. Qualitative and quantitative changes observed in humic fractions suggest that humified soil organic matter is a much more dynamic soil fraction than is normally considered and provides a utilizable energy reserve for soil microorganisms. Carbon levels can be successfully restored in soils through practices such as incorporation of crop residues, re\u2010vegetation and application of manures, biosolids and composts. Some amendments, such as olive mill waste compost, promote incorporation of altered lignin structures, N\u2010containing compounds and carbohydrates into humic acids. The mineral\u2010bound fraction of humic C also increases, after their addition, and contributes to the accumulation of the most inert soil C pools

Constraining the relative inclinations of the planets B and C of the millisecond pulsar PSR B1257+12

We investigate on the relative inclination of the planets B and C orbiting the pulsar PSR B1257+12 in connection with potential violations of the equivalence principle (Abridged).Comment: LaTex2e, 10 pages, 1 table, 3 figures, 17 references. Small stylistic changes. Version to appear in Journal of Astrophysics and Astronomy (JAA

X-ray spectra from magnetar candidates. I. Monte Carlo simulations in the non-relativistic regime

The anomalous X-ray pulsars and soft gamma-repeaters are peculiar high-energy sources believed to host a magnetar, i.e. an ultra-magnetized neutron star. Their persistent, soft X-ray emission (~1-10 keV)is usually modeled by the superposition of a blackbody and a power-law tail. It has been suggested that this spectrum forms as the thermal photons emitted by the star surface traverse the magnetosphere. Magnetar magnetospheres are likely different from those of ordinary radio-pulsars, since the external magnetic field may acquire a toroidal component as a consequence of the deformation of the star crust induced by the super-strong interior field. In turn, the magnetosphere will be permeated by currents that can boost primary photons through repeated scatterings. Here we present 3D Monte Carlo simulations of photon propagation in a twisted magnetosphere. Our model is based on a simplified treatment of the charge carriers velocity distribution which, however, accounts for the particle collective motion, in addition to the thermal one. Present treatment is restricted to conservative (Thomson) scattering in the electron rest frame. The code, nonetheless, is completely general and inclusion of the relativistic QED resonant cross section, which is required in the modeling of the hard (~20-200 keV) spectral tails observed in the magnetar candidates, is under way. The properties of emerging spectra have been assessed under different conditions, by exploring the model parameter space, including effects arising from the viewing geometry. Monte Carlo runs have been collected into a spectral archive. Two tabulated XSPEC spectral models, with and without viewing angles, have been produced and applied to the 0.1-10 keV XMM-Newton EPIC-pn spectrum of the AXP CXOU J1647-4552.Comment: 37 pages, 14 figures, 1 table; corrected typos; accepted for publication in MNRA