Differential effects on membrane permeability and viability of human keratinocyte cells undergoing very low intensity megasonic fields

Among different therapeutic applications of Ultrasound (US), transient membrane sonoporation (SP) - a temporary, non-lethal porosity, mechanically induced in cell membranes through US exposure - represents a compelling opportunity towards an efficient and safe drug delivery. Nevertheless, progresses in this field have been limited by an insufficient understanding of the potential cytotoxic effects of US related to the failure of the cellular repair and to the possible activation of inflammatory pathway. In this framework we studied the in vitro effects of very low-intensity US on a human keratinocyte cell line, which represents an ideal model system of skin protective barrier cells which are the first to be involved during medical US treatments. Bioeffects linked to US application at 1 MHz varying the exposure parameters were investigated by fluorescence microscopy and fluorescence activated cell sorting. Our results indicate that keratinocytes undergoing low US doses can uptake drug model molecules with size and efficiency which depend on exposure parameters. According to sub-cavitation SP models, we have identified the range of doses triggering transient membrane SP, actually with negligible biological damage. By increasing US doses we observed a reduced cells viability and an inflammatory gene overexpression enlightening novel healthy relevant strategies

Non-vascular interventional procedures: effective dose to patient and equivalent dose to abdominal organs by means of dicom images and Monte Carlo simulation

This study evaluates X-ray exposure in patient undergoing abdominal extra-vascular interventional procedures by means of Digital Imaging and COmmunications in Medicine (DICOM) image headers and Monte Carlo simulation. The main aim was to assess the effective and equivalent doses, under the hypothesis of their correlation with the dose area product (DAP) measured during each examination. This allows to collect dosimetric information about each patient and to evaluate associated risks without resorting to in vivo dosimetry. The dose calculation was performed in 79 procedures through the Monte Carlo simulator PCXMC (A PC-based Monte Carlo program for calculating patient doses in medical X-ray examinations), by using the real geometrical and dosimetric irradiation conditions, automatically extracted from DICOM headers. The DAP measurements were also validated by using thermoluminescent dosimeters on an anthropomorphic phantom. The expected linear correlation between effective doses and DAP was confirmed with an R(2) of 0.974. Moreover, in order to easily calculate patient doses, conversion coefficients that relate equivalent doses to measurable quantities, such as DAP, were obtained

Modified-release prednisone for polymyalgia rheumatica: a multicentre, randomised, active-controlled, double-blind, parallel-group study.

Objective: To assess the efficacy and safety of modified-release (MR) versus immediate-release (IR) prednisone in newly diagnosed glucocorticoid (GC)-na\uefve patients with polymyalgia rheumatica (PMR). Methods: Patients were randomised to double-blind MR prednisone (taken at approximately 22:00) or IR prednisone (taken in the morning), 15 mg/day for 4 weeks. The primary end point was complete response rate ( 6570% reduction in PMR visual analogue scale, duration of morning stiffness and C reactive protein (CRP) (or CRP < 2 7 upper limit of normal (ULN))) at week 4. Non-inferiority was decided if the lower 95% confidence limit (MR vs IR prednisone) was above -15%. 400 patients were planned but only 62 were enrolled due to difficulties in recruiting GC-na\uefve patients with PMR with CRP 652 7ULN. Results: The percentage of complete responders at week 4 was numerically greater for MR prednisone (53.8%) than for IR prednisone (40.9%). Non-inferiority of MR versus IR prednisone was not proven in the primary analysis on the per protocol population (N=48; treatment difference: 12.22%; 95% CI -15.82% to 40.25%). However, sensitivity analysis on the full analysis population showed an evident trend favouring MR prednisone (N=62; treatment difference: 15.56%; 95% CI -9.16% to 40.28%). Adverse events were generally mild and transient with no unexpected safety observations. Conclusions: The study showed a clear trend for favourable short-term efficacy of MR prednisone versus IR prednisone in early treatment of PMR. Further studies are warranted

Identification of the TeV Gamma-ray Source ARGO J2031+4157 with the Cygnus Cocoon

The extended TeV gamma-ray source ARGO J2031+4157 (or MGRO J2031+41) is positionally consistent with the Cygnus Cocoon discovered by $Fermi$-LAT at GeV energies in the Cygnus superbubble. Reanalyzing the ARGO-YBJ data collected from November 2007 to January 2013, the angular extension and energy spectrum of ARGO J2031+4157 are evaluated. After subtracting the contribution of the overlapping TeV sources, the ARGO-YBJ excess map is fitted with a two-dimensional Gaussian function in a square region of $10^{\circ}\times 10^{\circ}$, finding a source extension $\sigma_{ext}$= 1$^{\circ}$.8$\pm$0$^{\circ}$.5. The observed differential energy spectrum is $dN/dE =(2.5\pm0.4) \times 10^{-11}(E/1 TeV)^{-2.6\pm0.3}$ photons cm$^{-2}$ s$^{-1}$ TeV$^{-1}$, in the energy range 0.2-10 TeV. The angular extension is consistent with that of the Cygnus Cocoon as measured by $Fermi$-LAT, and the spectrum also shows a good connection with the one measured in the 1-100 GeV energy range. These features suggest to identify ARGO J2031+4157 as the counterpart of the Cygnus Cocoon at TeV energies. The Cygnus Cocoon, located in the star-forming region of Cygnus X, is interpreted as a cocoon of freshly accelerated cosmic rays related to the Cygnus superbubble. The spectral similarity with Supernova Remnants indicates that the particle acceleration inside a superbubble is similar to that in a SNR. The spectral measurements from 1 GeV to 10 TeV allows for the first time to determine the possible spectrum slope of the underlying particle distribution. A hadronic model is adopted to explain the spectral energy distribution.Comment: 16 pages, 3 figures, has been accepted by ApJ for publicatio

Quantifying bid-ask spreads in the Chinese stock market using limit-order book data: Intraday pattern, probability distribution, long memory, and multifractal nature

The statistical properties of the bid-ask spread of a frequently traded Chinese stock listed on the Shenzhen Stock Exchange are investigated using the limit-order book data. Three different definitions of spread are considered based on the time right before transactions, the time whenever the highest buying price or the lowest selling price changes, and a fixed time interval. The results are qualitatively similar no matter linear prices or logarithmic prices are used. The average spread exhibits evident intraday patterns consisting of a big L-shape in morning transactions and a small L-shape in the afternoon. The distributions of the spread with different definitions decay as power laws. The tail exponents of spreads at transaction level are well within the interval $(2,3)$ and that of average spreads are well in line with the inverse cubic law for different time intervals. Based on the detrended fluctuation analysis, we found the evidence of long memory in the bid-ask spread time series for all three definitions, even after the removal of the intraday pattern. Using the classical box-counting approach for multifractal analysis, we show that the time series of bid-ask spread does not possess multifractal nature.Comment: 8 EPJ pages including 7 eps figure

Fluid geochemistry of the Los Humeros geothermal field (LHGF - Puebla, Mexico): New constraints for the conceptual model

Geothermal power in Mexico is mainly produced in four geothermal fields operated by the Comision Federal de Electricidad (CFE): Cerro Prieto, Los Azufres, Los Humeros, and Las Tres Virgenes. The Los Humeros Geothermal Field (LHGF) is ranked third in terms of generated capacity, and in the last decade its installed capacity has doubled (up to 95.0 MW). Further increases in the geothermal power generation capacity in Mexico are planned, and thus the LHGF warrants further examination. The development and growth phases of any geothermal project must start from an awareness of the conceptual model of the natural system studied. The recharge mechanism, feeding zones, and fluid flow-path must be identified, along with the estimation of the temperature at the productive level and of phase separation (liquid - steam). To accomplish this, detailed fluid geochemical surveys were carried out in June 2017 and March 2018, in which 57 and 87 samples were collected, respectively, from cold and thermal springs, water wells and maar lakes located around and inside the LHGF. Samples from fumaroles inside the producing area were also collected for the first time, together with fluid from re-injection wells. The presence of a meteoric component, which plays an important role at the regional scale, is confirmed by the chemical and isotope data, and its contribution in terms of recharge may be higher than previously assumed. The Sierra Madre Oriental, on the west side of the LHGF, is characterized by widespread outcrops of limestone belonging to the same geological formation as those at the bottom of the LHGF. The isotope composition (delta D and delta O-18, respectively -77.3 parts per thousand and -10.50 parts per thousand for the hypothetical Infiltration Water IW) is similar to that observed in cold springs located in the Sierra Madre Oriental, and from this the evolution of isotopes in the liquid-rock-steam system during water-rock interaction and phase separation processes can be modelled. Thus, the experimental data obtained for natural gas emissions (fumarolic condensates) and for geothermal fluids can be reproduced. These findings suggest that geothermal fluids in the LHGF are likely to be derived from meteoric water infiltrating (IW) the limestone outcrops of the Sierra Madre Oriental. During their flow-path, the infiltrating waters exchange isotopes at a high temperature with the crustal rocks, which have a much higher O-18/O-16 ratio, resulting in a shift towards higher delta O-18 (-4.35 parts per thousand +/- 1) as the water O exchanges with rock O. The vapor phase can be separated from this deep water (DW) and it is discharged from the fumarolic effluents of Loma Blanca. Single Step Vapor Separation (SSVS) and Continuous Steam Separation processes (CSS) were modelled using stable isotopes of water. The results of geochemical modeling agree with available data for geothermal liquids discharged from several geothermal wells, suggesting that steam separation may be interpreted either as SSVS or CSS. Other processes can affect the chemistry and isotope composition of geothermal fluids (e.g. phase segregation, gas exchange, contributions from magmatic-volcanic deep fluids and re-injection fluids). The proposed conceptual model is consistent with both the geochemical data and the geological setting, and provides a useful point of reference for examining the fluid flow-path and geochemical processes active in the LHGF, at least at a general level. An involvement of magmatic-volcanic deep fluids in the feeding mechanism of the geothermal system cannot be excluded at priori, but the regional meteoric end-member is supported by the data and it seems the most important component

Comparison of the Diagnostic Accuracy of Serological and Histology Tests for Helicobacter Pylori in Patients with Dyspepsia and Metabolic Syndrome

Background: Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, especially in metabolic syndrome patients. The use of a accessible and easy diagnostic method, can speed up the treatment of this infection This study compared two methods of histology and serology for diagnosis of H. pylori in metabolic syndrome patients.Methods: This study was done on 175 metabolic syndrome patients with dyspepsia referred to Shahroud Imam Hossain hospital in 2014. From each patient, standard biopsy and serology tests were taken with endoscopy. This data will be analyzed with sensitivity, specificity, positive and negative predictive value.Results: Of the 175 patients studied, 90 (51.4%) were male and 85 (48.6%) were female. The mean patient age was 46.9±18.6 years. From 175 patients, 114(65.1%)  and 149 (85.3%) patients tested positive by serology and histology, respectively. For the serological test, sensitivity, specificity, positive predictive value and negative predictive value were 66.4%, 42.3%, 86.8%, and 18.1%. It was also found that with IgG values higher than 1.3, there was a sensitivity of 90.7%, and specificity of 72.8%, which was considered a positive test. The cut-off point performance test means that  maximum at this point with 78.3% the area under the curve (AUC),  there is the highest sensitivity and specificity.Conclusions: Due to the relative sensitivity and specificity of serological tests in comparison with other diagnostic methods as well as the simplicity, speed, and low cost, it is recommended that this test be used for screening metabolic syndrome patients