Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival

MAGnesium-oral supplementation to reduce PAin in patients with severe PERipheral arterial occlusive disease: the MAG-PAPER randomised clinical trial protocol

ntroduction Magnesium exerts analgaesic effects in several animal pain models, as well as in patients affected by acute postoperative pain and neuropathic chronic pain. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD). We describe the protocol of a single-centre randomised double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD. Methods and analysis Adult patients affected by PAOD at stages III and IV of Lèriche-Fontaine classification, who are opioid-naïve, and who have been admitted to our Acute Pain Service for intractable pain, will be eligible. Patients will be randomised to the control group, treated with standard therapy (oxycodone and pregabalin) plus placebo for 2 weeks, or to the experimental group (standard therapy plus magnesium oxide). Patients will be evaluated on days 0, 2, 4, 6, 8, 12 and 14; the following information will being collected: daily oxycodone dose; average and maximum pain (Numerical Rating Scale); pain relief (Pain Relief Scale); characteristics of the pain (Neuropathic Pain Scale); impact of pain on the patient's daily activities (Brief Pain Inventory). The primary outcome will be oxycodone dosage needed to achieve satisfactory analgaesia on day 14. Secondary outcomes will be pain relief on day 2, time needed to achieve satisfactory analgaesia and time needed to achieve a pain reduction of 50%. A sample size calculation was performed for the primary outcome, which estimated a required sample size of 150 patients (75 per group). Ethics and dissemination Ethical approval of the study protocol has been obtained from Comitato Etico Provinciale di Brescia, Brescia, Italy. Trial results will be disseminated through scientific journal manuscripts and scientific conference presentations. Trial registration number NCT02455726

Fabrication of Compliant and Transparent Hollow Cerebral Vascular Phantoms for In Vitro Studies Using 3D Printing and Spin–Dip Coating

Endovascular surgery through flow diverters and coils is increasingly used for the minimally invasive treatment of intracranial aneurysms. To study the effectiveness of these devices, in vitro tests are performed in which synthetic vascular phantoms are typically used to reproduce in vivo conditions. In this paper, we propose a manufacturing process to obtain compliant and transparent hollow vessel replicas to assess the mechanical behaviour of endovascular devices and perform flow measurements. The vessel models were obtained in three main steps. First, a mould was 3D-printed in a water-soluble material; two techniques, fusion deposition modelling and stereolithography, were compared for this purpose. Then, the mould was covered with a thin layer of silicone through spin-dip coating, and finally, when the silicone layer solidified, it was dissolved in a hot water bath. The final models were tested in terms of the quality of the final results, the mechanical properties of the silicone, thickness uniformity, and transparency properties. The proposed approach makes it possible to produce models of different sizes and complexity whose transparency and mechanical properties are suitable for in vitro experiments. Its applicability is demonstrated through idealised and patient-specific cases

Analysis of High Energy Impact of a Raindrop on Water

The present paper is devoted to the analysis of the impact of a raindrop on water. The studied configuration is focused on the effects of high energy splash regimes, caused by the impact of large droplets at high velocity. Such cases, which mimic raindrops falling on the surface of the ocean at their terminal speed, are characterized by short time scales and complex mechanisms, and they have received little attention until now. The GERRIS opensource solver is used to perform three-dimensional simulations of the impact. The capabilities of octree adaptative mesh refinement enable to capture the small-scale features of the flow, while the Volume Of Fluid (VOF) approach combined with a balanced force surface tension calculation is applied to advect the volume fraction of liquid and reconstruct the interfaces. A post-processing of the results has been developed to identify each object resulting from the splash and characterize their evolution in time. Specifically, the contour of the liquid/gas structure created at the impact is reconstructed as well as the size and position of the ligaments and droplets aerosolized in the atmosphere. The results are compared to experimental data obtained previously by Murphy et al. (J. Fluid Mech., vol. 780, pp. 536–577): both the crown formation above the cavity created by the impact, the ligaments emanating from the rim at the top of the crown, and the downward liquid jet that pierces through the bottom of the cavity, are correctly reproduced by the model. A very good quantitative agreement is also obtained regarding the time evolution of the crown dimensions, including its closure after the initial phase of expansion