Age-dependent skewing of X chromosome inactivation appears delayed in centenarians\u2019 offspring. Is there a role for allelic imbalance in Healthy Aging and Longevity?

Recently, it has been proposed that age-related X chromosome inactivation (XCI) skewing can clinically result in late-onset X-linked disorders. This observation leads to hypothesize that age-related skewed XCI might also influence lifespan in women. To investigate this issue, we employed a new experimental model of longevity and healthy aging including 55 female centenarians, 40 of their offspring, 33 age-matched offspring of both non-long-lived parents and 41 young women. Peripheral blood DNA from 169 females was screened for heterozygosity at the HUMARA locus. We confirmed that skewing of XCI is an age-dependent phenomenon. However, skewed XCI was significantly less severe and frequent in centenarians' offspring [degree of skewing (DS) = 0.16 \ub1 0.02] compared to age-matched offspring of both non-long-lived parents (DS = 0.24 \ub1 0.02) (P < 0.05). A second goal was to assess whether changes in XCI pattern could be a consequence of loss of methylation on X chromosome. Using a methylation array evaluating 1085 CpG sites across X chromosome and eleven CpG sites located at HUMARA locus, no differences in methylation levels and profiles emerged between all groups analysed, thus suggesting that age-associated epigenetic changes could not influence HUMARA results. In conclusion, the results presented herein highlight for the first time an interesting link between skewing of XCI and healthy aging and longevity. We speculate that the allelic imbalance produced by XCI skewing may compromise the cooperative and compensatory organization occurring between the two cell populations that make up the female mosaic

R-modes in Neutron Stars with Crusts: Turbulent Saturation, Spin-down, and Crust Melting

Rossby waves (r-modes) have been suggested as a means to regulate the spin periods of young or accreting neutron stars, and also to produce observable gravitational wave radiation. R-modes involve primarily transverse, incompressive motions of the star's fluid core. However, neutron stars gain crusts early in their lives: therefore, r-modes also imply shear in the fluid beneath the crust. We examine the criterion for this shear layer to become turbulent, and derive the rate of dissipation in the turbulent regime. Unlike dissipation from a viscous boundary layer, turbulent energy loss is nonlinear in mode energy and can therefore cause the mode to saturate at amplitudes typically much less than unity. This energy loss also reappears as heat below the crust. We study the possibility of crust melting as well as its implications for the spin evolution of low-mass X-ray binaries. Lastly, we identify some universal features of the spin evolution that may have observational consequences.Comment: 12 pages, 4 figures, submitted to Ap

Differences in visceral fat and fat bacterial colonization between ulcerative colitis and Crohn's disease. An in vivo and in vitro study

Crohn's disease (CD) is notably characterized by the expansion of visceral fat with small adipocytes expressing a high proportion of anti-inflammatory genes. Conversely, visceral fat depots in ulcerative colitis (UC) patients have never been characterized. Our study aims were a) to compare adipocyte morphology and gene expression profile and bacterial translocation in omental (OM) and mesenteric (MES) adipose tissue of patients with UC and CD, and b) to investigate the effect of bacterial infection on adipocyte proliferation in vitro. Specimens of OM and MES were collected from 11 UC and 11 CD patients, processed and examined by light microscopy. Gene expression profiles were evaluated in adipocytes isolated from visceral adipose tissue using microarray and RTqPCR validations. Bacteria within adipose tissue were immuno-detected by confocal scanning laser microscopy. Adipocytes were incubated with Enterococcus faecalis and cells counted after 24 h. Morphology and molecular profile of OM and MES revealed that UC adipose tissue is less inflamed than CD adipose tissue. Genes linked to inflammation, bacterial response, chemotaxis and angiogenesis were down-regulated in adipocytes from UC compared to CD, whereas genes related to metallothioneins, apoptosis pathways and growth factor binding were up-regulated. A dense perinuclear positivity for Enterococcus faecalis was detected in visceral adipocytes from CD, whereas positivity was weak in UC. In vitro bacterial infection was associated with a five-fold increase in the proliferation rate of OM preadipocytes. Compared to UC, visceral adipose tissue from CD is more inflamed and more colonized by intestinal bacteria, which increase adipocyte proliferation. The influence of bacteria stored within adipocytes on the clinical course of IBD warrants further investigation

Spatial structure of quark Cooper pairs in a color superconductor

Spatial structure of Cooper pairs with quantum numbers color 3^*, I=J=L=S=0 in ud 2 flavor quark matter is studied by solving the gap equation and calculating the coherence length in full momentum range without the weak coupling approximation. Although the gap at the Fermi surface and the coherence length depend on density weakly, the shape of the r-space pair wave function varies strongly with density. This result indicates that quark Cooper pairs become more bosonic at higher densities.Comment: 10 pages, 3 figures. The frequency dependence of the gap and the limitation on the type I/type II discussion are mentioned briefly. To appear in Phys. Rev.

Efficacy of a preparation based on calcium butyrate, bifidobacterium bifidum, bifidobacterium lactis, and fructooligosaccharides in the prevention of relapse in ulcerative colitis: A prospective observational study

Several compounds based on short chain fatty acids and/or probiotics/prebiotics have shown promising results in the therapy of ulcerative colitis (UC), possibly due to its key role in restoring gut homeostasis as well as intestinal barrier integrity. Here, we investigated the efficacy of a patented preparation based on calcium butyrate, Bifidobacterium bifidum, Bifidobacterium lactis, and fructooligosaccharides (FEEDColon(®), Princeps, Cuneo, Italy) in maintaining remission and improving subjective symptoms and inflammatory indices in patients with UC receiving 5-ASA therapy. A total of 42 patients were prospectively recruited and randomized in 21 patients receiving combination therapy with mesalamine (5-ASA) plus FEEDColon(®) and 21 patients treated with standard 5-ASA therapy. Patients were assessed at baseline, at 6-month, and 12-month follow-up (FU). Therapeutic success (defined as Mayo partial score ≤ 2 and faecal calprotectin (FC) < 250 µg/g at 12-month FU) was reached by 32 (76%) patients: 20 (95%) among those treated with 5-ASA + FeedColon(®), and 12 (57%) among those treated with 5-ASA only (p = 0.009). Consistently, patients treated with combination therapy improved subjective symptoms (quality of life, abdominal pain, and stool consistency) and reduced FC values, while those treated with 5-ASA alone, improved neither subjective symptoms nor FC during the FU. In conclusion, FEEDColon(®) supplementation appears to be a valid add-on therapy for the maintenance of remission in patients with UC. Further multicentre, placebo-controlled, double-blind clinical trials are needed to validate our results on larger cohorts of patients with UC

Evaluation of expressive writing for postpartum health: A randomized controlled trial

Pregnancy, birth and adjusting to a new baby is a potentially stressful time that can negatively affect the health of women. There is some evidence that expressive writing can have positive effects on psychological and physical health, particularly during stressful periods. The current study aimed to evaluate whether expressive writing would improve women’s postpartum health. A randomized controlled trial was conducted with three conditions: expressive writing (n=188), a control writing task (n=213), or normal care (n=163). Measures of psychological health, physical health and quality of life were measured at baseline (6-12 weeks postpartum), 1 month and 6 months later. Ratings of stress were taken before and after the expressive writing task. Intent-to-treat analyses showed no significant differences between women in the expressive writing, control writing and normal care groups on measures of physical health, anxiety, depression, mood or quality of life at 1 and 6 months. Uptake and adherence to the writing tasks was low. However, women in the expressive writing group rated their stress as significantly reduced after completing the task. Cost analysis suggest women who did expressive writing had the lowest costs in terms of healthcare service use and lowest cost per unit of improvement in quality of life. Results suggest expressive writing is not effective as a universal intervention for all women 6-12 weeks postpartum. Future research should examine expressive writing as a targeted intervention for women in high-risk groups, such as those with mild or moderate depression, and further examine cost-effectiveness

Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: The effect of different substitution patterns

New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)- glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking analysis allowed to identify several key features of the binding mode of such compounds to the protease

Reliability of an isometric and isokinetic strength testing protocol of the knee and ankle in young adults

Background: Isokinetic dynamometers are becoming very common in assessing muscle strength and pathology, both in research and clinical practice, but for most of those devices reliability studies are still needed to support their extended use. The aim of this study is to assess the test-retest reliability also in health adults. Methods: Thirty adults (13 male and 17 females; mean age 25.4 ± 2.7 years) were recruited among University students. They participated to two testing sessions (7 day apart) in which they performed isokinetic and isometric strength assessment of the knee and ankle flexion and extension. Results: All variable showed an Intra-class correlation coefficient higher than 0.7 (isometric knee extension 0.96; isokinetic knee extension 0.96; isokinetic knee flexion 0.97; isometric ankle right flexion pl and flexion do 0.75-0.96; isometric ankle left flexion pl and flexion do 0.78-0.97; isokinetic ankle right flexion pl and flexion do 0.88-0.73; isokinetic ankle right flexion pl and flexion do 0.88-0.85) and paired-sample t-test showed no significant difference. Moreover, most of the recorded values were included within the upper and lower limits of agreement. Conclusion: Multi-joint evaluation system is a reliable device to assess knee and ankle isokinetic and isometric strength among healthy adults

Muons and emissivities of neutrinos in neutron star cores

In this work we consider the role of muons in various URCA processes relevant for neutrino emissions in the core region of neutron stars. The calculations are done for $\beta$--stable nuclear matter with and without muons. We find muons to appear at densities $\rho = 0.15$ fm$^{-3}$, slightly around the saturation density for nuclear matter $\rho_0 =0.16$ fm$^{-3}$. The direct URCA processes for nucleons are forbidden for densities below $\rho = 0.5$ fm$^{-3}$, however the modified URCA processes with muons $(n+N\rightarrow p+N +\mu +\overline{\nu}_{\mu}, p+N+\mu \rightarrow n+N+\nu_{\mu}$), where $N$ is a nucleon, result in neutrino emissivities comparable to those from $(n+N\rightarrow p+N +e +\overline{\nu}_e, p+N+e \rightarrow n+N+\nu_e$). This opens up for further possibilities to explain the rapid cooling of neutrons stars. Superconducting protons reduce however these emissivities at densities below $0.4$ fm$^{-3}$.Comment: 14 pages, Revtex style, 3 uuencoded figs include