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

The sequential price of anarchy for atomic congestion games

In situations without central coordination, the price of anarchy relates the quality of any Nash equilibrium to the quality of a global optimum. Instead of assuming that all players choose their actions simultaneously, here we consider games where players choose their actions sequentially. The sequential price of anarchy, recently introduced by Paes Leme, Syrgkanis, and Tardos then relates the quality of any subgame perfect equilibrium to the quality of a global optimum. The effect of sequential decision making on the quality of equilibria, however, depends on the specific game under consideration.\ud Here we analyze the sequential price of anarchy for atomic congestion games with affine cost functions. We derive several lower and upper bounds, showing that sequential decisions mitigate the worst case outcomes known for the classical price of anarchy. Next to tight bounds on the sequential price of anarchy, a methodological contribution of our work is, among other things, a "factor revealing" integer linear programming approach that we use to solve the case of three players

Diagnosing acute kidney injury ahead of time in critically ill septic patients using kinetic estimated glomerular filtration rate

Introduction: Accurate and actionable diagnosis of Acute Kidney Injury (AKI) ahead of time is important to prevent or mitigate renal insufficiency. The purpose of this study was to evaluate the performance of Kinetic estimated Glomerular Filtration Rate (KeGFR) in timely predicting AKI in critically ill septic patients. Methods: We conducted a retrospective analysis on septic ICU patients who developed AKI in AmsterdamUMCdb, the first freely available European ICU database. The reference standard for AKI was the Kidney Disease: Improving Global Outcomes (KDIGO) classification based on serum creatinine and urine output (UO). Prediction of AKI was based on stages defined by KeGFR and UO. Classifications were compared by length of ICU stay (LOS), need for renal replacement therapy and 28-day mortality. Predictive performance and time between prediction and diagnosis were calculated. Results: Of 2492 patients in the cohort, 1560 (62.0%) were diagnosed with AKI by KDIGO and 1706 (68.5%) by KeGFR criteria. Disease stages had agreement of kappa = 0.77, with KeGFR sensitivity 93.2%, specificity 73.0% and accuracy 85.7%. Median time to recognition of AKI Stage 1 was 13.2 h faster for KeGFR, and 7.5 h and 5.0 h for Stages 2 and 3. Outcomes revealed a slight difference in LOS and 28-day mortality for Stage 1. Conclusions: Predictive performance of KeGFR combined with UO criteria for diagnosing AKI is excellent. Compared to KDIGO, deterioration of renal function was identified earlier, most prominently for lower stages of AKI. This may shift the actionable window for preventing and mitigating renal insufficiency

The qq-boson-fermion realizations of quantum suprealgebra Uq(gl(2/1))U_q(gl(2/1))

We show that our construction of realizations for Lie algebras and quantum algebras can be generalized to quantum superalgebras, too. We study an example of quantum superalgebra $U_q(gl(2/1))$ and give the boson-fermion realization with respect to one pair od q-deformed boson operator and 2 pairs of fermions.Comment: 8 page

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]

Language of CTO interventions – Focus on hardware

AbstractThe knowledge of variety of chronic total occlusion (CTO) hardware and the ability to use them represents the key to success of any CTO interventions. However, the multiplicity of CTO hardware and their physical character and the terminology used by experts create confusion in the mind of an average interventional cardiologist, particularly a beginner in this field. This knowledge is available but is scattered. We aim to classify and compare the currently used devices based on their properties focusing on how physical character of each device can be utilized in a specific situation, thus clarifying and simplifying the technical discourse

Mid‐Holocene site formation, diagenesis and human activity at the foothills of Serra da Estrela (Portugal)

UIDB/00749/2020 UIDP/00749/2020The Neolithic occupation of Penedo dos Mouros in the foothills of Serra da Estrela, Portugalʼs highest mountain, dates to the 5th to 4th millennia cal B.C. The siteʼs faunal assemblage is extremely rare in the regional prehistoric archaeological record, due to the acidity of the granitic geology. This underlines Penedo dos Mouros importance as a reference site for understanding early pastoralism in the region. Due to the insufficient survival of bone collagen for radiocarbon dating and the homogeneity of the stratigraphy, where most visible contacts are due to postdepositional processes, we chose micromorphology to address the reasons behind the bone preservation and to assess the stratigraphic integrity of the prehistoric deposit. Reworking of eroding saprolitic soils was a major factor in the sediment accumulation, with remains of short human occupation events. Possible evidence for clearance fires linked to the first occurrences of pastoralism practised in the region, creating open spaces for grazing, was identified. Post‐depositional carbonate cementation derived from ashes, identifiable at the microscopic scale, enabled bone preservation. Carbonate and spodic‐like features document water saturation once the sedimentation ceased. This sedimentary dynamic has broader geomorphological implications, such as an inferred post‐Neolithic incision of the stream valley adjacent to the site.publishersversionpublishe

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