Towards Dead Time Inclusion in Neuronal Modeling

A mathematical description of the refractoriness period in neuronal diffusion modeling is given and its moments are explicitly obtained in a form that is suitable for quantitative evaluations. Then, for the Wiener, Ornstein-Uhlenbeck and Feller neuronal models, an analysis of the features exhibited by the mean and variance of the first passage time and of refractoriness period is performed.Comment: 12 pages, 1 figur

Preparation of Drug-Loaded PLGA-PEG Nanoparticles by Membrane-Assisted Nanoprecipitation

Purpose: The aim of this work is to develop a scalable continuous system suitable for the formulation of polymeric nanoparticles using membrane-assisted nanoprecipitation. One of the hurdles to overcome in the use of nanostructured materials as drug delivery vectors is their availability at industrial scale. Innovation in process technology is required to translate laboratory production into mass production while preserving their desired nanoscale characteristics. Methods: Membrane-assisted nanoprecipitation has been used for the production of Poly(D, L lactide-co-glycolide)-co-poly ethylene glycol] diblock) (PLGA-PEG) nanoparticles using a pulsed back-and-forward flow arrangement. Tubular Shirasu porous glass membranes (SPG) with pore diameters of 1 and 0.2 µm were used to control the mixing process during the nanoprecipitation reaction. Results: The size of the resulting PLGA-PEG nanoparticles could be readily tuned in the range from 250 to 400 nm with high homogeneity (PDI lower than 0.2) by controlling the dispersed phase volume/continuous phase volume ratio. Dexamethasone was successfully encapsulated in a continuous process, achieving an encapsulation efficiency and drug loading efficiency of 50% and 5%, respectively. The dexamethasone was released from the nanoparticles following Fickian kinetics. Conclusions: The method allowed to produce polymeric nanoparticles for drug delivery with a high productivity, reproducibility and easy scalability

Does Ionized Magnesium Offer a Different Perspective Exploring the Association between Magnesemia and Targeted Cardiovascular Risk Factors?

Evidence of the association of magnesium (Mg) with arterial stiffness has so far been conflicting. The interplay between hypertension and elevated body mass index (BMI), with hypomagnesemia, instead, has been described in the literature in a more consistent way. Our study aims at revisiting the correlations between blood Mg levels and hemodynamic and body composition parameters in the general population, exploring the sensitivity profile of ionized Mg (Ion-Mg) compared to total Mg (Tot-Mg). We collected data from 755 subjects randomly chosen from a Swiss population previously described and stratified our sample into four equivalent classes according to ionized (whole blood) and total (serum) magnesium. After correcting for age, statistically significant differences emerged between: (i) Tot-Mg ≤ 0.70 and 0.81 ≤ Tot-Mg ≤ 0.90 for cf-PWV (p = 0.039); (ii) Tot-Mg ≤ 0.70 and Tot-Mg ≥ 0.91 for o-PWV (p = 0.046). We also found a statistically significant difference among groups of Ion-Mg values for the 24 h extremes of systolic blood pressure (p = 0.048) and among groups of Tot-Mg for BMI (p = 0.050). Females showed significantly lower levels of total magnesium (p = 0.035) and ionized magnesium (p < 0.001) than males. The overall agreement between magnesium analysis methods was 64% (95%CI: 60.8−67.7%). Our results confirm that Ion-Mg compared with Tot-Mg offers a different profile in detecting both correlations with hemodynamic and body composition parameters and dysmagnesemias. Lower levels of magnesium were associated with worse arterial aging parameters, larger 24 h blood pressure excursions, and higher BMI. Ion-Mg was superior in detecting the correlation with blood pressure only. Considering Ion-Mg as a more specific marker of the magnesium status, and the partially contradictory results of our explorative cross-sectional study, to avoid confounding factors and misinterpretations, ionized magnesium should be used as reference in future studies

Effectiveness of a Hydrophilic Curcumin-Based Formulation in Coadjuvating the Therapeutic Effect of Intravitreal Dexamethasone in Subjects With Diabetic Macular Edema

Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME). Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety. Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T0 to the 6 months’ evaluation was significant (p = 0.00). The mean CRT result was significantly different at month 4 (p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls. Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings

A double-ended queue with catastrophes and repairs, and a jump-diffusion approximation

Consider a system performing a continuous-time random walk on the integers, subject to catastrophes occurring at constant rate, and followed by exponentially-distributed repair times. After any repair the system starts anew from state zero. We study both the transient and steady-state probability laws of the stochastic process that describes the state of the system. We then derive a heavy-traffic approximation to the model that yields a jump-diffusion process. The latter is equivalent to a Wiener process subject to randomly occurring jumps, whose probability law is obtained. The goodness of the approximation is finally discussed.Comment: 18 pages, 5 figures, paper accepted by "Methodology and Computing in Applied Probability", the final publication is available at http://www.springerlink.co

Electrical storm: A clinical and electrophysiological overview

Electrical storm (ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverterdefibrillator (ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia (VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment

Design, optimization and experimental characterization of RF injectors for high brightness electron beams and plasma acceleration

In this article, we share our experience related to the new photo-injector commissioning at the SPARC\_LAB test facility. The new photo-injector was installed into an existing machine and our goal was not only to improve the final beam parameters themselves but to improve the machine handling in day-to-day operations as well. Thus, besides the pure beam characterization, this article contains information about the improvements, that were introduced into the new photo-injector design from the machine maintenance point of view, and the benefits, that we gained by using the new technique to assemble the gun itself

Temperature stress differentially modulates transcription in meiotic anthers of heat-tolerant and heat-sensitive tomato plants

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