Ex vivo gene therapy to produce bone using different cell types

Gene therapy and tissue engineering promise to revolutionize orthopaedic surgery. This study comprehensively compares five different cell types in ex vivo gene therapy to produce bone. The cell types include a bone marrow stromal cell line, primary muscle derived cells, primary bone marrow stromal cells, primary articular chondrocytes, and primary fibroblasts. After transduction by an adenovirus encoding for bone morphogenetic protein-2, all of the cell types were capable of secreting bone morphogenetic protein-2. However, the bone marrow stromal cell line and muscle derived cells showed more responsiveness to recombinant human bone morphogenetic protein-2 than did the other cell types. In vivo injection of each of the cell populations transduced to secrete bone morphogenetic protein-2 resulted in bone formation. Radiographic and histologic analyses corroborated the in vitro data regarding bone morphogenetic protein-2 secretion and cellular osteocompetence. This study showed the feasibility of using primary bone marrow stromal cells, primary muscle derived cells, primary articular chondrocytes, primary fibroblasts, and an osteogenesis imperfecta stromal cell line in ex vivo gene therapy to produce bone. The study also showed the advantages and disadvantages inherent in using each cell type.     

Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler

Objectives To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high‐dose disposable Twincer? dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Methods Comparison of predicted flow and particle behaviour from CFD computations with experimental data obtained with cascade impactor and laser diffraction analysis. Key findings Inhaler resistance, flow split, particle trajectories and particle residence times can well be predicted with CFD for a multiple classifier based inhaler like the Twincer?. CFD computations showed that the flow split of the Twincer? is independent of the pressure drop across the inhaler and that the total flow rate can be decreased without affecting the dispersion efficacy or retention behaviour. They also showed that classifier symmetry can be improved by reducing the resistance of one of the classifier bypass channels, which for the current concept does not contribute to the swirl in the classifier chamber. Conclusions CFD is a highly valuable tool for development and optimisation of dry powder inhalers. CFD can assist adapting the inhaler design to specific physico‐chemical properties of the drug formulation with respect to dispersion and retention behaviour.     

Hautkrankheiten Akute und chronische Infektionskrankheiten

Ohne Zusammenfassung     

Erythematöse,ekzematöse,parenchymatöse Entzündungsprocesse

Ohne Zusammenfassung     

Bericht über die Verhandlungen des VI. Congresses der Deutschen dermatologischen Gesellschaft am 31. Mai, 1. und 2. Juni 1898 in Strassburg i/E

Archives of Dermatological Research -     

Medicaid care management: Description of high-cost addictions treatment clients

High utilizers of alcohol and other drug treatment (AODTx) services are a priority for healthcare cost control. We examine characteristics of Medicaid-funded AODTx clients, comparing three groups: individuals < 90th percentile of AODTx expenditures (n = 41,054); high-cost clients in the top decile of AODTx expenditures (HC; n = 5,718); and 1760 enrollees in a chronic care management (CM) program for HC clients implemented in 22 counties in New York State. Medicaid and state AODTx registry databases were combined to draw demographic, clinical, social needs and treatment history data. HC clients accounted for 49% of AODTx costs funded by Medicaid. As expected, HC clients had significant social welfare needs, comorbid medical and psychiatric conditions, and use of inpatient services. The CM program was successful in enrolling some high-needs, high-cost clients but faced barriers to reaching the most costly and disengaged individuals.     

Influence of Humans on Evolution and Mobilization of Environmental Antibiotic Resistome

The clinical failure of antimicrobial drugs that were previously effective in controlling infectious disease is a tragedy of increasing magnitude that gravely affects human health. This resistance by pathogens is often the endpoint of an evolutionary process that began billions of years ago in non–disease-causing microorganisms. This environmental resistome, its mobilization, and the conditions that facilitate its entry into human pathogens are at the heart of the current public health crisis in antibiotic resistance. Understanding the origins, evolution, and mechanisms of transfer of resistance elements is vital to our ability to adequately address this public health issue.