Efficacy and safety of intravenous nerinetide initiated by paramedics in the field for acute cerebral ischaemia within 3 h of symptom onset (FRONTIER): a phase 2, multicentre, randomised, double-blind, placebo-controlled study.

Background: Nerinetide is a neuroprotectant effective in preclinical models of acute ischaemic stroke when administered within 3 h of onset. However, the clinical evaluation of neuroprotectants in this short timeframe is challenging. We sought to establish the feasibility, safety, and effectiveness of nerinetide when given before hospital arrival within 3 h of symptom onset of suspected stroke.

Concise review: role of mesenchymal stem cells in wound repair.

Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC), which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat.

Treatment of inflammatory diseases with mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) are rare progenitor cells present in adult bone marrow that have the capacity to differentiate into a variety of tissue types, including bone, cartilage, tendon, fat, and muscle. In addition to multilineage differentiation capacity, MSCs regulate immune and inflammatory responses, providing therapeutic potential for treating diseases characterized by the presence of an inflammatory component. The availability of bone marrow and the ability to isolate and expand hMSCs ex vivo make these cells an attractive candidate for drug development.

Expression patterns of a circadian clock gene are associated with age-related polyethism in harvester ants, Pogonomyrmex occidentalis.

Background: Recent advances in sociogenomics allow for comparative analyses of molecular mechanisms regulating the development of social behavior. In eusocial insects, one key aspect of their sociality, the division of labor, has received the most attention. Age-related polyethism, a derived form of division of labor in ants and bees where colony tasks are allocated among distinct behavioral phenotypes, has traditionally been assumed to be a product of convergent evolution.

Anatomically shaped osteochondral constructs for articular cartilage repair.

Few successful treatment modalities exist for surface-wide, full-thickness lesions of articular cartilage. Functional tissue engineering offers a great potential for the clinical management of such lesions. Our long-term hypothesis is that anatomically shaped tissue constructs of entire articular layers can be engineered in vitro on a bony substrate, for subsequent implantation.

Disparate aggrecan gene expression in chondrocytes subjected to hypotonic and hypertonic loading in 2D and 3D culture.

The effects of hypotonic (180 mOsm) and hypertonic (580 mOsm) medium loading on chondrocyte aggrecan gene expression in 2D monolayer and 3D hydrogel culture (agarose or alginate) were studied. Aggrecan promoter activity was monitored using a luciferase reporter gene assay and transient transfection. Osmotic loading was observed to differentially affect promoter activity, with hypotonic loading generally producing at least a 40% elevation in promoter activity, except for the case of alginate where a 50% suppression was observed.

Experimental and biphasic FEM determinations of the material properties and hydraulic permeability of the meniscus in tension.

Tensile tests and biphasic finite element modeling were used to determine a set of transversely isotropic properties for the meniscus, including the hydraulic permeability coefficients and solid matrix properties. Stress-relaxation tests were conducted on planar samples of canine meniscus samples of different orientations, and the solid matrix properties were determined from equilibrium data. A 3-D linear biphasic and tranversely isotropic finite element model was developed to model the stress-relaxation behavior of the samples in tension, and optimization was used to determine the permeability coefficients, k1 and k2, governing fluid flow parallel and perpendicular to the collagen fibers, respectively.