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

Combined use of x-ray fluorescence microscopy, phase contrast imaging for high resolution quantitative iron mapping in inflamed cells

X-ray fluorescence microscopy (XRFM) is a powerful technique to detect and localize elements in cells. To derive information useful for biology and medicine, it is essential not only to localize, but also to map quantitatively the element concentration. Here we applied quantitative XRFM to iron in phagocytic cells. Iron, a primary component of living cells, can become toxic when present in excess. In human fluids, free iron is maintained at 10-18 M concentration thanks to iron binding proteins as lactoferrin (Lf). The iron homeostasis, involving the physiological ratio of iron between tissues/secretions and blood, is strictly regulated by ferroportin, the sole protein able to export iron from cells to blood. Inflammatory processes induced by lipopolysaccharide (LPS) or bacterial pathoge inhibit ferroportin synthesis in epithelial and phagocytic cells thus hindering iron export, increasing intracellular iron and bacterial multiplication. In this respect, Lf is emerging as an important regulator of both iron and inflammatory homeostasis. Here we studied phagocytic cells inflamed by bacterial LPS and untreated or treated with milk derived bovine Lf. Quantitative mapping of iron concentration and mass fraction at high spatial resolution is obtained combining X-ray fluorescence microscopy, atomic force microscopy and synchrotron phase contrast imaging

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

Co-Incineration of Textile ETP Sludge in Captive Power House Boiler

The ETP Sludge generated by Raymond Textile Ltd.  Boregaon District – Chhindwara India is Co-incinerated in the Captive Power House Boiler in irreversible and environmental sound manner without influencing emissions on partial replacement of traditial fuel. Co-incineration benefits upgrade waste management, reduce environmental impacts, improver the industrial sector’s competitiveness decreases largely the cost of waste management of ETP sludge. The analysis results of the stack parameters revealed that the emission values are well below the standards set by Central Pollution Control Board for the common Hazardous Waste Incinerations. The Captive Power House perforce requires high temperature in the boiler around 10000C. Such high temperature conditions ensure no noxious emission during the co-incineration of the waste materials.ÂÂ

Elastic geobarometry for anisotropic inclusions in cubic hosts

Mineral inclusions entrapped in other minerals may record the local stresses at the moment of their entrapment in the deep Earth. When rocks are exhumed to the surface of the Earth, residual stresses and strains may still be preserved in the inclusion. If measured and interpreted correctly through elastic geobarometry, they give us invaluable information on the pressures (P) and temperatures (T) of metamorphism. Current estimates of P and T of entrapment rely on simplified models that assumes that the inclusion is spherical and embedded in an infinite host, and that their elastic properties are isotropic. We report a new method for elastic geobarometry for anisotropic inclusions in quasi-isotropic hosts. The change of strain in the inclusion is modelled with the axial equations of state of the host and the inclusion. Their elastic interaction is accounted for by introducing a 4th rank tensor, the relaxation tensor, that can be evaluated numerically for any symmetry of the host and the inclusion and for any geometry of the system. This approach can be used to predict the residual strain/stress state developed in an inclusion after exhumation from known entrapment conditions, or to estimate the entrapment conditions from the residual strain measured in real inclusions. In general, anisotropic strain and stress states are developed in non-cubic mineral inclusions such as quartz and zircon, with deviatoric stresses typically limited to few kbars. For garnet hosts, the effect of the mutual crystallographic orientation between the host and the inclusion on the residual strain and stress is negligible when the inclusion is spherical and isolated. Assuming external hydrostatic conditions, our results suggest that the isotropic and the new anisotropic models give estimations of entrapment conditions within 2%