A nonparametric approach for model individualization in an artificial pancreas

The identification of patient-tailored linear time invariant glucose-insulin models is investigated for type 1 diabetic patients, that are characterized by a substantial inter-subject variability. The individualized linear models are identified by considering a novel kernel-based nonparametric approach and are compared with a linear time invariant average model in terms of prediction performance by means of the coefficient of determination, fit, positive and negative max errors, and root mean squared error. Model identification and validation are based on in-silico data collected from the adult virtual population of the UVA/Padova simulator. The data generation involves a protocol designed to produce a sufficient input excitation without compromising patient safety, compatible also with real life scenarios. The identified models are exploited to synthesize an individualized Model Predictive Controller (MPC) for each patient, which is used in an Artificial Pancreas to maintain the blood glucose concentration within an euglycemic range. The MPC used in several clinical studies, synthesized on the basis of a non-individualized average linear time invariant model, is also considered as reference. The closed-loop control performance is evaluated in an in-silico study on the adult virtual population of the UVA/Padova simulator in a perturbed scenario, in which the MPC is blind to random variations of insulin sensitivity in each virtual patient. © 2015, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved

Building a biomimetic membrane for neutron reflectivity investigation : complexity, asymmetry and contrast

The preparation and investigation of model membranes is deserving growing interest both for the physics of complex systems, and for biology. The need of simplified models should preserve mimicking the qualifying characteristics of biological membranes, and keep non-invasive and detailed description. As a main feature, biological membranes are non-homogeneous in the disposition of components, both in the lateral and in the transverse direction. We prepared asymmetric supported membranes containing GM1 ganglioside in biomimetic proportion according to different protocols. Then, we studied their internal structure by neutron reflectometry, providing few-Angstrom sensitivity in the cross direction meanwhile avoiding radiation damage. This technique can also be profitably applied to study interactions at the membrane surface. The best protocol has proven to be the Langmuir-Blodgett/Langmuir-Schaefer depositions. Notably, also the simpler and most accessible protocol of vesicle fusion was found to be suitable for straightforward and good quality deposition of compositionally asymmetric membranes

Polystyrene perturbs the structure, dynamics, and mechanical properties of DPPC membranes: An experimental and computational study

Synthetic plastic oligomers can interact with the cells of living organisms by different ways. They can be intentionally administered to the human body as part of nanosized biomedical devices. They can be inhaled by exposed workers, during the production of multicomponent, polymer-based nanocomposites. They can leak out of food packaging. Most importantly, they can result from the degradation of plastic waste, and enter the food chain. A physicochemical characterization of the effects of synthetic polymers on the structure and dynamics of cell components is still lacking. Here, we combine a wide spectrum of experimental techniques (calorimetry, x-ray, and neutron scattering) with atomistic Molecular Dynamics simulations to study the interactions between short chains of polystyrene (25 monomers) and model lipid membranes (DPPC, in both gel and fluid phase). We find that doping doses of polystyrene oligomers alter the thermal properties of DPPC, stabilizing the fluid lipid phase. They perturb the membrane structure and dynamics, in a concentration-dependent fashion. Eventually, they modify the mechanical properties of DPPC, reducing its bending modulus in the fluid phase. Our results call for a systematic, interdisciplinary assessment of the mechanisms of interaction of synthetic, everyday use polymers with cell membranes

Parental evaluation of a telemonitoring service for children with Type 1 Diabetes

Introduction In the past years, we developed a telemonitoring service for young patients affected by Type 1 Diabetes. That service provides data to the clinical staff and offers an important tool to the parents, that are able to oversee in real time their children. The aim of this work was to analyze the parents' perceived usefulness of the service. Methods The service was tested by the parents of 31 children enrolled in a seven-day clinical trial during a summer camp. To study the parents' perception we proposed and analyzed two questionnaires. A baseline questionnaire focused on the daily management and implications of their children's diabetes, while a post-study one measured the perceived benefits of telemonitoring. Questionnaires also included free text comment spaces. Results Analysis of the baseline questionnaires underlined the parents' suffering and fatigue: 51% of total responses showed a negative tendency and the mean value of the perceived quality of life was 64.13 in a 0-100 scale. In the post-study questionnaires about half of the parents believed in a possible improvement adopting telemonitoring. Moreover, the foreseen improvement in quality of life was significant, increasing from 64.13 to 78.39 ( p-value\u2009=\u20090.0001). The analysis of free text comments highlighted an improvement in mood, and parents' commitment was also proved by their willingness to pay for the service (median\u2009=\u2009200\u2009euro/year). Discussion A high number of parents appreciated the telemonitoring service and were confident that it could improve communication with physicians as well as the family's own peace of mind

The nasal delivery of nanoencapsulated statins – An approach for brain delivery

© 2016 Clementino et al. Purpose: Along with their cholesterol-lowering effect, statins have shown a wide range of pleiotropic effects potentially beneficial to neurodegenerative diseases. However, such effects are extremely elusive via the conventional oral administration. The purpose of the present study was to prepare and characterize the physicochemical properties and the in vivo biodistribution of simvastatin-loaded lecithin/chitosan nanoparticles (SVT-LCNs) suitable for nasal administration in view of an improved delivery of the statins to the brain. Materials and methods: Chitosan, lecithin, and different oil excipients were used to prepare nanocapsules loaded with simvastatin. Particle size distribution, surface charge, structure, simvastatin loading and release, and interaction with mucus of nanoparticles were determined. The nanoparticle nasal toxicity was evaluated in vitro using RPMI 2651 nasal cell lines. Finally, in vivo biodistribution was assessed by gamma scintigraphy via Tc99m labeling of the particles. Results: Among the different types of nanoparticles produced, the SVT-LCN_MaiLab showed the most ideal physicochemical characteristics, with small diameter (200 nm), positive surface charge (+48 mV) and high encapsulation efficiency (EE; 98%). Size distribution was further confirmed by nanoparticle tracking analysis and electron microscopy. The particles showed a relatively fast release of simvastatin in vitro (35.6%±4.2% in 6 hours) in simulated nasal fluid. Blank nanoparticles did not show cytotoxicity, evidencing that the formulation is safe for nasal administration, while cytotoxicity of simvastatin-loaded nanoparticles (IC50) was found to be three times lower than the drug solution (9.92 vs 3.50 μM). In rats, a significantly higher radioactivity was evidenced in the brain after nasal delivery of simvastatin-loaded nanoparticles in comparison to the administration of a similar dose of simvastatin suspension. Conclusion: The SVT-LCNs developed presented some of the most desirable characteristics for mucosal delivery, that is, small particle size, positive surface charge, long-term stability, high EE, and mucoadhesion. In addition, they displayed two exciting features: First was their biodegradability by enzymes present in the mucus layer, such as lysozyme. This indicates a new Trojan-horse strategy which may enhance drug release in the proximity of the nasal mucosa. Second was their ability to enhance the nose-to-brain transport as evidenced by preliminary gamma scintigraphy studies

Toxoplasma gondii infection in patients with hematological malignancies.

Toxoplasmosis is one of the most common parasitic infections in humans, but in most cases it does not cause serious illness; this protozoan can nevertheless cause devastating disease in immunocompromised hosts such as HIV-positive individuals. Only rarely is toxoplasmosis documented in hematological patients, and among them, those who undergo a transplant procedure are more frequently affected. In a retrospective multicenter survey, we collected data on six cases of toxoplasmosis in hematological patients. In the majority of cases, patients had undergone transplant procedures (five had undergone autologous or allogeneic transplantation). This complication needed special care in diagnosis, usually based on serology, neuroradiology, and PCR examination. However, in our experience the appropriate therapeutic approach was successful in the majority of cases

Cellular Biomechanic Impairment in Cardiomyocytes Carrying the Progeria Mutation: An Atomic Force Microscopy Investigation

Given the clinical effect of progeria syndrome, understanding the cell mechanical behavior of this pathology could benefit the patient's treatment. Progeria patients show a point mutation in the lamin A/C gene (LMNA), which could change the cell's biomechanical properties. This paper reports a mechano-dynamic analysis of a progeria mutation (c.1824 C > T, p.Gly608Gly) in neonatal rat ventricular myocytes (NRVMs) using cell indentation by atomic force microscopy to measure alterations in beating force, frequency, and contractile amplitude of selected cells within cell clusters. Furthermore, we examined the beating rate variability using a time-domain method that produces a Poincaré plot because beat-to-beat changes can shed light on the causes of arrhythmias. Our data have been further related to our cell phenotype findings, using immunofluorescence and calcium transient analysis, showing that mutant NRVMs display changes in both beating force and frequency. These changes were associated with a decreased gap junction localization (Connexin 43) in the mutant NRVMs even in the presence of a stable cytoskeletal structure (microtubules and actin filaments) when compared with controls (wild type and non-treated cells). These data emphasize the kindred between nucleoskeleton (LMNA), cytoskeleton, and the sarcolemmal structures in NRVM with the progeria Gly608Gly mutation, prompting future mechanistic and therapeutic investigations