Wynnmcdonald0119

Brain disorders tend to impact on many different regions in a typical way alterations do not spread randomly; rather, they seem to follow specific patterns of propagation that show a strong overlap between different pathologies. The insular cortex is one of the brain areas more involved in this phenomenon, as it seems to be altered by a wide range of brain diseases. On these grounds we thoroughly investigated the impact of brain disorders on the insular cortices analyzing the patterns of their structural co-alteration. We therefore investigated, applying a network analysis approach to meta-analytic data, 1) what pattern of gray matter alteration is associated with each of the insular cortex parcels; 2) whether or not this pattern correlates and overlaps with its functional meta-analytic connectivity; and, 3) the behavioral profile related to each insular co-alteration pattern. All the analyses were repeated considering two solutions one with two clusters and another with three. Our study confirmed that the insular cortex is one of the most altered cerebral regions among the cortical areas, and exhibits a dense network of co-alteration including a prevalence of cortical rather than sub-cortical brain regions. Regions of the frontal lobe are the most involved, while occipital lobe is the less affected. Furthermore, the co-alteration and co-activation patterns greatly overlap each other. These findings provide significant evidence that alterations caused by brain disorders are likely to be distributed according to the logic of network architecture, in which brain hubs lie at the center of networks composed of co-altered areas. For the first time, we shed light on existing differences between insula sub-regions even in the pathoconnectivity domain.Powder feeding is a crucial unit operation in continuous manufacturing (CM) of pharmaceutical products. Twin-screw feeders are typically employed to ensure the accurate mass flow of pharmaceutical materials throughout the production process. Here, contact and separation of particles can give rise to electrostatic charges, affecting feeder performance and final product quality. The knowledge of the material charging tendency would therefore be beneficial for both formulation and process design. At the early stage of product development, only a limited amount of material is available and the propensity of the powders to charge needs to be assessed on lab test equipment, which not necessarily represent the material state during processing. In this study, the tribo-charging behaviour of a set of common pharmaceutical materials (i.e., microcrystalline cellulose, D-mannitol, paracetamol and magnesium stearate) was experimentally evaluated. To this end, powder materials were let to flow over the stainless-steel pipes of the GranuCharge™ instrument. The resulting charge was compared to the one acquired during twin-screw feeding. In both cases, paracetamol exhibited the highest charging tendency followed by D-mannitol and microcrystalline cellulose and last by magnesium stearate. A good correlation was found for charge values obtained for both methods, despite the different tribo-charging mechanisms involved in the two set-ups. However, these differences in experimental set-ups led to diverse magnitudes and, in one case, polarity of charge. Additionally, an extensive material characterization was performed on the selected powders and results were statistically analyzed to identify critical material attributes (CMAs) affecting powder tribo-charging. A strong correlation was obtained between the measured charge and inter-particle friction. This indicated the latter as one of the most influencing material characteristic impacting the powder tribo-charging phenomenon of the selected materials.Small interfering RNA (siRNA) therapy has significant potential for the treatment of myriad diseases, including cancer. While intravenous routes of delivery have been found to be effective for efficient targeting to the liver, achieving high accumulations selectively in other organs, including lung tissues, can be a challenge. selleck compound We demonstrate the rational design and engineering of a layer-by-layer (LbL) nanoparticle-containing aerosol that is able to achieve efficient, multistage delivery of siRNA in vitro. For the purpose, LbL nanoparticles were, for the first time, encapsulated in composite porous micro scale particles using a supercritical CO2-assisted spray drying (SASD) apparatus using chitosan as an excipient. Such particles exhibited aerodynamic properties highly favorable for pulmonary administration, and effective silencing of mutant KRAS in lung cancer cells derived from tumors of a non-small cell lung cancer (NSCLC) autochthonous model. Furthermore, efficient alveolar accumulation following inhalation in healthy mice was also observed, corroborating in vitro aerodynamic results, and opening new perspectives for further studies of effective lung therapies These results show that multistage aerosols assembled by supercritical CO2-assisted spray drying can enable efficient RNA interference therapy of pulmonary diseases including lung cancer.The paper concerns the modelling of the passive solute transport through porous membranes. A general scheme for the mass transport has been developed upon the mixed diffusion-advection-reaction model. The passive advection has been introduced as a certain simplification of the Navier-Stokes problem, involving a pressure gradient-induced creeping flow of an incompressible Newtonian fluid. Nine scenarios for the drug transport process have been tested versus two experimental datasets acquired earlier (photoacoustic depth-profiling and contact angle surface wettability techniques) for the characterization of bulk and interfacial processes in a model pharmaceutical system the synthetic dodecanol-collodion porous membrane in contact with a photodegradable pigment dithranol. The scenarios considered include three mass transport models (the diffusion-advection-reaction, diffusion-advection and diffusion-reaction models) under three distinct types of the lower (the donor/acceptor interface) boundary conditions the Dirichlet-type instantaneous source, the Dirichlet-type interface relaxation, and the Neumann-type concentration gradient.