Safety and efficacy of endovascular treatment for carotid artery stenoses using proximal protection systems: 30-day follow-up

Introduction. Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, carotid artery stenting (CAS) with use of proximal protection systems (PPS) plays an important role as alternative treatment modality, especially in high risk patients. This study was aimed at the assessment of safety of CAS with use of the PPS and also at identification of risk factors associated with this procedure. Material and methods. This was a post hoc analysis, with 30-day follow-up. We analysed results of treatment of 94 patients who underwent 97 CAS with PPS, 47 such procedures in asymptomatic, and 50 in symptomatic individuals. Results. There were 0 strokes during 30-day follow-up. Transient ischaemic attacks occurred in 2 patients (2%) in symptomatic group. Risk factors of these adverse events comprised: tortuosity of the managed artery, chronic obstructive pulmonary disease, long lesion of the internal carotid artery and history of myocardial infarction. Conclusions. CAS with the use of PPS seems to be a relatively very safe procedure in high risk patients.Introduction. Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, carotid artery stenting (CAS) with use of proximal protection systems (PPS) plays an important role as alternative treatment modality, especially in high risk patients. This study was aimed at the assessment of safety of CAS with use of the PPS and also at identification of risk factors associated with this procedure. Material and methods. This was a post hoc analysis, with 30-day follow-up. We analysed results of treatment of 94 patients who underwent 97 CAS with PPS, 47 such procedures in asymptomatic, and 50 in symptomatic individuals. Results. There were 0 strokes during 30-day follow-up. Transient ischaemic attacks occurred in 2 patients (2%) in symptomatic group. Risk factors of these adverse events comprised: tortuosity of the managed artery, chronic obstructive pulmonary disease, long lesion of the internal carotid artery and history of myocardial infarction. Conclusions. CAS with the use of PPS seems to be a relatively very safe procedure in high risk patients

Imidazolidine-4-one derivatives in the search for novel chemosensitizers of Staphylococcus aureus MRSA : synthesis, biological evaluation and molecular modeling studies

A series of amine derivatives of 5-aromatic imidazolidine-4-ones (7–19), representing three subgroups: piperazine derivatives of 5-arylideneimidazolones (7–13), piperazine derivatives of 5-arylideneimidazolidine-2,4-dione (14–16) and primary amines of 5-naphthyl-5-methylimidazolidine-2,4-diones (17–19), was evaluated for their ability to improve antibiotics effectiveness in two strains of Gram-positive Staphylococcus aureus: ATCC 25923 (a reference strain) and MRSA (methicillin resistant S. aureus) HEMSA 5 (a resistant clinical isolate). The latter compounds (17–19) were obtained by 4-step synthesis using Bucherer-Bergs condensation, two-phase bromoalkylation and Gabriel reactions. The naphthalen derivative: (Z)-5-(naphthalen-2-ylmethylene)-2-(piperazin-1-yl)-3H-imidazol-4(5H)-one (10) was the most potent in combination with β-lactam antibiotics and ciprofloxacin against the resistant strain. The high potency to increase efficacy of oxacillin was noted for (Z)-5-(anthracen-10-ylmethylene)-2-(piperazin-1-yl)-3H-imidazol-4(5H)one (12) too. In order to explain the mechanism of action of the compounds 10 and 12, docking studies with the use of crystal structures of a penicillin binding protein (PBP2a) and MecR1 were carried out. Their outcomes suggested that the most probable mechanism of action of the active compounds is the interaction with MecR1. Molecular dynamic experiments performed for the active compounds and compound 13 (structurally similar to 12) supported this hypothesis and provided possible explanation of activity dependencies of the tested compounds in terms of the restoration of antibiotic efficacy in S. aureus MRSA HEMSA 5

Development of a PbWO4 Detector for Single-Shot Positron Annihilation Lifetime Spectroscopy at the GBAR Experiment

We have developed a PbWO4 (PWO) detector with a large dynamic range to measure the intensity of a positron beam and the absolute density of the ortho-positronium (o-Ps) cloud it creates. A simulation study shows that a setup based on such detectors may be used to determine the angular distribution of the emission and reflection of o-Ps to reduce part of the uncertainties of the measurement. These will allow to improve the precision in the measurement of the cross-section for the (anti)hydrogen formation by (anti)proton-positronium charge exchange and to optimize the yield of antihydrogen ion which is an essential parameter in the GBAR experiment

Low-basicity 5-HT7 receptor agonists synthesized using the van Leusen multicomponent protocol

A series of 5-aryl-1-alkylimidazole derivatives was synthesized using the van Leusen multicomponent reaction. The chemotype is the first example of low-basicity scaffolds exhibiting high affinity for 5-HT7 receptor together with agonist function. The chosen lead compounds 3-(1-ethyl-1H-imidazol-5-yl)-5- iodo-1H-indole (AGH-107, 1o, Ki 5-HT7=6nM, EC50=19nM, 176-fold selectivity over 5-HT1AR) and 1e (5-methoxy analogue, Ki 5-HT7=30nM, EC50=60nM) exhibited high selectivity over related CNS targets, high metabolic stability and low toxicity in HEK-293 and HepG2 cell cultures. A rapid absorption to the blood, high blood-brain barrier permeation and a very high peak concentration in the brain (Cmax=2723 ng/g) were found for 1o after i.p. (5mg/kg) administration in mice. The compound was found active in novel object recognition test in mice, at 0.5, 1 and 5mg/kg. Docking to 5-HT7R homology models indicated a plausible binding mode which explain the unusually high selectivity over the related CNS targets. Halogen bond formation between the most potent derivatives and the receptor is consistent with both the docking results and SAR. 5-Chlorine, bromine and iodine substitution resulted in a 13, 27 and 89-fold increase in binding affinities, respectively, and in enhanced 5-HT1AR selectivity

Est locus uni cuique suus: City and Status in Horace’s Satires 1.8 and 1.9

This is the published version

A 16 Parts per Trillion Comparison of the Antiproton-to-Proton q/m Ratios

The Standard Model (SM) of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning-trap systems. For instance, we compared the proton/antiproton magnetic moments with 1.5 ppb fractional precision, which improved upon previous best measurements by a factor of >3000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16ppt. Our result is based on the combination of four independent long term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental setups incorporating different systematic effects. The final result, $-(q/m)_{\mathrm{p}}/(q/m)_{\bar{\mathrm{p}}}$ = $1.000\,000\,000\,003 (16)$, is consistent with the fundamental charge-parity-time (CPT) reversal invariance, and improves the precision of our previous best measurement by a factor of 4.3. The measurement tests the SM at an energy scale of $1.96\cdot10^{-27}\,$GeV (C$.$L$.$ 0.68), and improves 10 coefficients of the Standard Model Extension (SME). Our cyclotron-clock-study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEP$_\text{cc}$) for antimatter to a level of $|\alpha_{g}-1| < 1.8 \cdot 10^{-7}$, and enables the first differential test of the WEP$_\text{cc}$ using antiprotons \cite{hughes1991constraints}. From this interpretation we constrain the differential WEP$_\text{cc}$-violating coefficient to $|\alpha_{g,D}-1|<0.030$

Ultra thin polymer foil cryogenic window for antiproton deceleration and storage

We present the design and characterisation of a cryogenic window based on an ultra-thin aluminised PET foil at T < 10K, which can withstand a pressure difference larger than 1bar at a leak rate < $1\times 10^{-9}$ mbar$\cdot$ l/s. Its thickness of approximately 1.7 $\mu$m makes it transparent to various types of particles over a broad energy range. To optimise the transfer of 100keV antiprotons through the window, we tested the degrading properties of different aluminium coated PET foils of thicknesses between 900nm and 2160nm, concluding that 1760nm foil decelerates antiprotons to an average energy of 5 keV. We have also explicitly studied the permeation as a function of coating thickness and temperature, and have performed extensive thermal and mechanical endurance and stress tests. Our final design integrated into the experiment has an effective open surface consisting of 7 holes with 1 mm diameter and will transmit up to 2.5% of the injected 100keV antiproton beam delivered by the AD/ELENA-facility of CERN