Biology and Treatment of Multiple Myeloma

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Quantification of earthquake diagnostic effects to assess low macroseismic intensities

AbstractA large amount of data about earthquake effects, supplied by citizens through a web-based questionnaire, enabled the analysis of the occurrence of many of the effects on humans and objects listed in macroseismic scales descriptions. Regarding the other diagnostic effects (rattling, moving, shifting, falling or overturning depending of the object type of doors, windows, china, glasses, small objects, pictures, vases, books, as well as frightened people and animal behaviour), data from more than 300,000 questionnaires about earthquakes felt in Italy from June 2007 to August 2017, were analysed by stacking them together as a function of hypocentral distance and magnitude. The comparison of the resulting percentages with the intensity prediction equation showed that almost all the chosen effects are good diagnostics for macroseismic intensity evaluation, as their percentages are well differentiated. We did not analyse the oscillations of hanging objects and liquids because the differences in effect attenuations, highlighted by the maps of the occurrence percentage, suggested to not consider them as diagnostic effect. This result allowed us to quantify the occurrence of each diagnostic effect for the intensity degrees from II to VI of the European macroseismic scale for the people who felt the earthquake. The application of the intensity assessment method to internet macroseismic data, based on the specifications herein proposed, should mitigate the problem of "not felt" undersampling in crowdsourced web data

Visual Field Loss Progression after Macular Hole Surgery

Purpose. To report a patient who experienced visual field loss progression after vitrectomy for an idiopathic stage II macular hole. Methods. Case report. A 68-year-old woman, with no history of glaucoma or any neuroophthalmological diseases, underwent a vitrectomy for a macular hole. Results. The patient showed macular hole closure and a resulting central visual acuity of 20/20. However, two months after surgery, she developed an inferotemporal visual field defect. Moreover, seven months after surgery, the patient noticed an enlargement of the temporal blind area: a nearly complete temporal defect was confirmed on visual field testing. Conclusions. Although the beneficial results of successfully treated macular holes are unquestionable, this report raises the possibility that visual field defects following macular hole surgery may be progressive

Influence of strong electromagnetic discharges on the dynamics of earthquakes time distribution in the Bishkek test area (Central Asia)

From 08/01/1983 to 28/03/1990, at the Bishkek ElectroMagnetic (EM) test site (Northern Tien Shan and Chu Val- ley area, Central Asia), strong currents, up to 2.5 kA, were released at a 4.5 km long electrical (grounded) dipole. This area is seismically active and a catalogue with about 14100 events from 1975 to 1996 has been analyzed. The seismic catalogue was divided into three parts: 1975-1983 first part with no EM experiments, 1983-1990 second part during EM experiments and 1988-1996 after experiments part. Qualitative and quantitative time series non- lin- ear analysis was applied to waiting times of earthquakes to the above three sub catalogue periods. The qualitative approach includes visual inspection of reconstructed phase space, Iterated Function Systems (IFS) and Recurrence Quantification Analysis (RQA). The quantitative approach followed correlation integral calculation of reconstruct- ed phase space of waiting time distribution, with noise reduction and surrogate testing methods. Moreover the Lem- pel-Ziv algorithmic complexity measure (LZC) was calculated. General dynamics of earthquakes' temporal distri- bution around the test area, reveals properties of low dimensional non linearity. Strong EM discharges lead to the increase in extent of regularity in earthquakes temporal distribution. After cessation of EM experiments the earth- quakes' temporal distribution becomes much more random than before experiments. To avoid non valid conclusions several tests were applied to our data set: differentiation of the time series was applied to check results not affected by non stationarity; the surrogate data approach was followed to reject the hypothesis that dynamics belongs to the colored noise type. Small earthquakes, below completeness threshold, were added to the analysis to check results robustness

Apoferritin nanocage as streptomycin drug reservoir: Technological optimization of a new drug delivery system

The aim of this study is to formulate and characterize streptomycin-loaded apoferritin nanoparticles (ApoStrep NPs) for their potential therapeutic use in bacterial resistant infections (i.e. tuberculosis). ApoStrep NPs were prepared by disassembly/reassembly process via pH method and changing apoferritin/drug molar ratio, purified by dialyses process also associated with gel filtration chromatography and characterized in their chemico-physical and technological parameters as yield, size distribution, polidispersivity, morphology, internal structure, zeta potential and loading efficacy. The results showed that spherical reproducible NPs could be obtained by using apoferritin/drug molar ratio lower than 1:25 and purification based on the combination of dialysis and gel filtration chromatography. Photon correlation spectroscopy, Uv–visible detection and electron microscopy showed the maintenance of the native apoferritin chemico-physical properties and structure. When formulated with apoferritin/drug 1:10 and 1:25 molar ratio, ApoStrep NPs showed remarkable encapsulation efficacy (35% and 28%, respectively) along with kinetic profile of drug delivery, approximately 15% at 37 °C in 72 h, as evidenced by “in vitro” release experiments

AFM/TEM complementary structural analysis of surface-functionalized nanoparticles

In the field of nanomedicine, the characterization of functionalized drug delivery systems, introduced on market as efficacious and selective therapeutics, represents a pivotal aspect of great importance. In particular, the morphology of polymeric nanoparticles, the most studied nanocarriers, is frequently assessed by transmission electron microscopy (TEM). Despite of TEM high resolution and versatility, this technology is frequently hampered by both the complicated procedure for sample preparation and the operative condition of analysis. Considering the scanning probe microscopies, atomic force microscopy (AFM) represents an extraordinary tool for the detailed characterization of submicron-size structure as the surface functionalization at the atomic scale. In this paper we discussed the advantage and limits of these microscopies applied to the characterization of PLGA nanoparticles functionalized with three different kinds of ligands (carbohydrate ligand, an antibody and quantum dots crystals) intentionally designed, created and tailored with specific physico-chemical properties to meet the needs of specific applications (targeting or imaging)

PEGylated siRNA lipoplexes for silencing of BLIMP-1 in Primary Effusion Lymphoma: In vitro evidences of antitumoral activity

Silencing of the B lymphocyte-induced maturation protein 1 (Blimp-1), a pivotal transcriptional regulator during terminal differentiation of B cells into plasma cells with siRNAs is under investigation as novel therapeutic approach in Primary Effusion Lymphoma (PEL), a HHV-8 related and aggressive B cell Lymphoma currently lacking of an efficacious therapeutic approach. The clinical application of small interfering RNA (siRNA) in cancer therapy is limited by the lack of an efficient systemic siRNA delivery system. In this study we aim to develop pegylated siRNA lipoplexes formed using the cationic lipid DOTAP and DSPE-PEG2000, capable to effectively stabilize anti-Blimp-1 siRNA and suitable for systemic administration. Two types of pegylated lipoplexes using a classic (C-PEG Lipoplexes) or a post-pegylation method (P-PEG-Lipoplexes) were formulated and compared in their physicochemical properties (size, zeta potential, morphology and structure) and efficiency on PEL cell lines. A stable siRNAs protection was obtained with post pegylation approach (2% molar of DSPE-PEG2000 with respect to lipid) resulting in structures with diameters of 300 nm and a complexation efficiency higher that 80% (0.08 nmol/10 nmol of lipid). In vitro studies on PEL cell lines suggested that empty liposomes were characterized by a low cell toxicity also after PEG modification (cell viability and cell density over 85% after treatment with 10 μM of lipid). We demonstrated that P-PEG-Lipoplexes were able to significantly reduce the levels of BLIMP-1 protein leading to reduction of viability (less that 15% after transfection with 100 nM of complexed siRNAs) and activation of apoptosis. In vitro efficiency encourages us to further test the in vivo potential of P-PEG-Lipoplexes in PEL therapy