Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program

OBJECTIVE: Endothelial dysfunction (ED) predisposes to venous thrombosis (VT) and post-thrombotic syndrome (PTS), a long-term VT-related complication. Sulodexide (SDX) is a highly purified glycosaminoglycan with antithrombotic, pro-fibrinolytic and anti-inflammatory activity used in the treatment of chronic venous disease (CVD), including patients with PTS. SDX has recently obtained clinical evidence in the “extension therapy” after initial-standard anticoagulant treatment for the secondary prevention of recurrent deep vein thrombosis (DVT). Herein, we investigated how SDX counteracts ED. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used. Metabolic and non metabolic-induced ED was induced by treating with methylglyoxal (MGO) or irradiation (IR), respectively. Bafilomycin A1 was used to inhibit autophagy. The production of reactive oxygen species (ROS), tetrazolium bromide (MTT) assay for cell viability, terminal de-oxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for cell apoptosis, Real-time PCR and Western blot analysis for gene and protein expression were used. RESULTS: SDX protected HUVEC from MGO- or IR-induced apoptosis by counteracting the activation of the intrinsic and extrinsic caspase cascades. The cytoprotective effects of SDX resulted from a reduction in a) ROS production, b) neo-synthesis and release of pro-inflammatory cytokines (TNFα, IL1, IL6, IL8), c) DNA damage induced by MGO or IR. These effects were reduced when autophagy was inhibited. CONCLUSIONS: Data herein collected indicate the ability of SDX to counteract ED induced by metabolic or non-metabolic stresses by involving the intracellular autophagy pathway. Our experience significantly increases the knowledge of the mechanisms of action of SDX against ED and supports the use of SDX in the treatment of CVD, PTS and in the secondary prevention of recurrent DVT

Ligation of the intersphincteric fistula tract (LIFT) to treat anal fistula: early results from a prospective observational study

Ligation of the intersphincteric tract (LIFT), a novel sphincter-saving technique, has been recently described with promising results. Literature data are still scant. In this prospective observational study, we present our experience with this technique

Single hole dynamics in the t-J model on a square lattice

We present quantum Monte Carlo (QMC) simulations for a single hole in a t-J model from J=0.4t to J=4t on square lattices with up to 24 x 24 sites. The lower edge of the spectrum is directly extracted from the imaginary time Green's function. In agreement with earlier calculations, we find flat bands around $(0,\pm\pi)$, $(\pm\pi,0)$ and the minimum of the dispersion at $(\pm\pi/2,\pm\pi/2)$. For small J both self-consistent Born approximation and series expansions give a bandwidth for the lower edge of the spectrum in agreement with the simulations, whereas for J/t > 1, only series expansions agree quantitatively with our QMC results. This band corresponds to a coherent quasiparticle. This is shown by a finite size scaling of the quasiparticle weight $Z(\vec k)$ that leads to a finite result in the thermodynamic limit for the considered values of $J/t$. The spectral function $A(\vec k, \omega)$ is obtained from the imaginary time Green's function via the maximum entropy method. Resonances above the lowest edge of the spectrum are identified, whose J-dependence is quantitatively described by string excitations up to J/t=2

ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study.

BACKGROUND: In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program. PATIENTS AND METHODS: Patients should be younger than 65 years with unfavorable stage IA and IIA HL (i.e. stage IA or IIA with bulky disease and/or subdiaphragmatic disease, erythrocyte sedimentation rate higher than 40, extranodal (E) involvement, hilar involvement and more than three involved lymph node areas). RESULTS: Ninety-two patients were allocated to the ABVD arm and 89 to the EVE arm. Complete remission (CR) rates at the end of treatment program [chemotherapy (CT) + RT] were 93% and 92% for ABVD and EVE arms, respectively (P = NS). The 5-year relapse-free survival (RFS) rate was 95% for ABVD and 78% for EVE (P < 0.05). As a consequence of the different relapse rate, the 5-year failure-free survival (FFS) rate was significantly better for ABVD (90%) than for EVE (73%) arm (P < 0.05). No differences in terms of overall survival (OS) were observed for the two study arms. CONCLUSIONS: In unfavorable stage IA and IIA HL patients, no differences were observed between ABVD and EVE arms in terms of CR rate and OS. EVE CT, however, was significantly worse than ABVD in terms of RFS and FFS and cannot be recommended as initial treatment for HL

Prospects for K+→π+ννˉK^+ \to \pi^+ \nu \bar{ \nu } at CERN in NA62

The NA62 experiment will begin taking data in 2015. Its primary purpose is a 10% measurement of the branching ratio of the ultrarare kaon decay $K^+ \to \pi^+ \nu \bar{ \nu }$, using the decay in flight of kaons in an unseparated beam with momentum 75 GeV/c.The detector and analysis technique are described here.Comment: 8 pages for proceedings of 50 Years of CP

Quantum Monte Carlo simulations of infinitely strongly correlated fermions

Numerical simulations of the two-dimensional t-J model in the limit $J/t \ll 1$ are performed for rather large systems (up to $N = 12 \times 12$) using a world-line loop-algorithm. It is shown that in the one-hole case with J=0, where no minus signs appear, very low temperatures ($\beta t \sim 3000$) are necessary in order to reach Nagaoka's state. J/t \ltsim 0.05 leads to the formation of partially polarized systems, whereas J/t \gtsim 0.05 corresponds to minimal spin. The two-hole case shows enhanced total spin up to the lowest attainable temperatures ($\beta t = 150$).Comment: 6 pages, 5 figure

Density of a gas of spin polarized fermions in a magnetic field

For a fermion gas with equally spaced energy levels that is subjected to a magnetic field, the particle density is calculated. The derivation is based on the path integral approach for identical particles, in combination with the inversion techniques for the generating function of the static response functions. Explicit results are presented for the ground state density as a function of the magnetic field with a number of particles ranging from 1 to 45.Comment: 9 pages, 8 figures; To appear in Phys. Rev. E on December 1, 2000; e-mail addresses: [email protected], [email protected], [email protected], [email protected]

Should I stay or should I go? Sibling effects in household formation

This paper analyzes peer effects among siblings in the decision to leave parental home. Estimating peer effects is challenging because of problems of refection, endogenous group formation, and correlated unobservables. We overcome these issues using the exogenous variation in siblings' household formation implied by the eligibility rules for a Spanish rental subsidy. Our results show that sibling effects are negative and that these effects can be explained by the presence of old or ill parents. Sibling effects turn positive from older to younger close-in-age siblings, when imitation is more likely to prevail. Our findings indicate that policy makers who aim at fostering household formation should target the household rather than the individual and combine policies for young adults with policies for the elderly

Context Matters: The Illusive Simplicity of Macaque V1 Receptive Fields

Even in V1, where neurons have well characterized classical receptive fields (CRFs), it has been difficult to deduce which features of natural scenes stimuli they actually respond to. Forward models based upon CRF stimuli have had limited success in predicting the response of V1 neurons to natural scenes. As natural scenes exhibit complex spatial and temporal correlations, this could be due to surround effects that modulate the sensitivity of the CRF. Here, instead of attempting a forward model, we quantify the importance of the natural scenes surround for awake macaque monkeys by modeling it non-parametrically. We also quantify the influence of two forms of trial to trial variability. The first is related to the neuron’s own spike history. The second is related to ongoing mean field population activity reflected by the local field potential (LFP). We find that the surround produces strong temporal modulations in the firing rate that can be both suppressive and facilitative. Further, the LFP is found to induce a precise timing in spikes, which tend to be temporally localized on sharp LFP transients in the gamma frequency range. Using the pseudo R[superscript 2] as a measure of model fit, we find that during natural scene viewing the CRF dominates, accounting for 60% of the fit, but that taken collectively the surround, spike history and LFP are almost as important, accounting for 40%. However, overall only a small proportion of V1 spiking statistics could be explained (R[superscript 2]~5%), even when the full stimulus, spike history and LFP were taken into account. This suggests that under natural scene conditions, the dominant influence on V1 neurons is not the stimulus, nor the mean field dynamics of the LFP, but the complex, incoherent dynamics of the network in which neurons are embedded.National Institutes of Health (U.S.) (K25 NS052422-02)National Institutes of Health (U.S.) (DP1 ODOO3646

Quantum phases and phase transitions of Mott insulators

This article contains a theoretical overview of the physical properties of antiferromagnetic Mott insulators in spatial dimensions greater than one. Many such materials have been experimentally studied in the past decade and a half, and we make contact with these studies. The simplest class of Mott insulators have an even number of S=1/2 spins per unit cell, and these can be described with quantitative accuracy by the bond operator method: we discuss their spin gap and magnetically ordered states, and the transitions between them driven by pressure or an applied magnetic field. The case of an odd number of S=1/2 spins per unit cell is more subtle: here the spin gap state can spontaneously develop bond order (so the ground state again has an even number of S=1/2 spins per unit cell), and/or acquire topological order and fractionalized excitations. We describe the conditions under which such spin gap states can form, and survey recent theories (T. Senthil et al., cond-mat/0312617) of the quantum phase transitions among these states and magnetically ordered states. We describe the breakdown of the Landau-Ginzburg-Wilson paradigm at these quantum critical points, accompanied by the appearance of emergent gauge excitations.Comment: 51 pages, 13 figure