Targeting specific brain districts for advanced nanotherapies: A review from the perspective of precision nanomedicine.

Numerous studies are focused on nanoparticle penetration into the brain functionalizing them with ligands useful to cross the blood-brain barrier. However, cell targeting is also crucial, given that cerebral pathologies frequently affect specific brain cells or areas. Functionalize nanoparticles with the most appropriate targeting elements, tailor their physical parameters, and consider the brain's complex anatomy are essential aspects for precise therapy and diagnosis. In this review, we addressed the state of the art on targeted nanoparticles for drug delivery in diseased brain regions, outlining progress, limitations, and ongoing challenges. We also provide a summary and overview of general design principles that can be applied to nanotherapies, considering the areas and cell types affected by the most common brain disorders. We then emphasize lingering uncertainties that hinder the translational possibilities of nanotherapies for clinical use. Finally, we offer suggestions for continuing preclinical investigations to enhance the overall effectiveness of precision nanomedicine in addressing neurological conditions. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Determinants of bone damage: An ex-vivo study on porcine vertebrae.

Bone's resistance to fracture depends on several factors, such as bone mass, microarchitecture, and tissue material properties. The clinical assessment of bone strength is generally performed by Dual-X Ray Photon Absorptiometry (DXA), measuring bone mineral density (BMD) and trabecular bone score (TBS). Although it is considered the major predictor of bone strength, BMD only accounts for about 70% of fragility fractures, while the remaining 30% could be described by bone "quality" impairment parameters, mainly related to tissue microarchitecture. The assessment of bone microarchitecture generally requires more invasive techniques, which are not applicable in routine clinical practice, or X-Ray based imaging techniques, requiring a longer post-processing. Another important aspect is the presence of local damage in the bony tissue that may also affect the prediction of bone strength and fracture risk. To provide a more comprehensive analysis of bone quality and quantity, and to assess the effect of damage, here we adopt a framework that includes clinical, morphological, and mechanical analyses, carried out by means of DXA, µCT and mechanical compressive testing, respectively. This study has been carried out on trabecular bones, taken from porcine trabecular vertebrae, for the similarity with human lumbar spine. This study confirms that no single method can provide a complete characterization of bone tissue, and the combination of complementary characterization techniques is required for an accurate and exhaustive description of bone status. BMD and TBS have shown to be complementary parameters to assess bone strength, the former assessing the bone quantity and resistance to damage, and the latter the bone quality and the presence of damage accumulation without being able to predict the risk of fracture.

Quantifying established clinical assessment measures using 3D-movement analysis in individuals with Down syndrome.

PURPOSE: A movement protocol for quantifying functional limitation in people with Down syndrome (DS) during the execution of a series of range of motion (ROM) tasks has been developed as a new assessment approach, combining quantitative measures of movement analysis and functional mobility with clinically established qualitative motor skill assessments. METHODS: Fifteen subjects with DS and 11 subjects with typical development were evaluated using this movement protocol. RESULTS: The results revealed longer durations in execution across all tasks in the DS group and were most likely due to low muscular tone and poor coordination. A significant difference in ankle ROM was found in the DS group during leg-lifting, with a wide plantar-flexion demonstrated during the entire movement. This result may be associated with the typical strategy for foot contact that generally favours the toe. Significant differences were also found in the trunk ROM and in the knee ROM and may likely reflect an increase of agonist-antagonist co-contraction, a strategy that may modify stability and dynamic equilibrium. CONCLUSION: The combined quantitative/qualitative protocol is an important advancement in evaluating individuals with DS and should be integrated into a more comprehensive evaluation of dynamic gait and lower limb analysis.

A facile stereoselective synthesis of alpha-glycosyl ureas.

Alpha-glycosyl ureas can be synthesised directly from tetra-O-benzyl glycosyl azides and isocyanates, using a one-pot procedure that is simple and general in scope. The benzyl protecting groups are easily removed from the urea products by catalytic hydrogenation. The synthesised alpha-glycosyl ureas represent a new class of neo-glycoconjugates with the potential of being resistant towards carbohydrate processing enzymes.