138 research outputs found
What is the future of targeted therapy in rheumatology: biologics or small molecules?
Background: Until late in the 20th century, the therapy of rheumatic diseases relied on the use of drugs that had been developed through empirical approaches without detailed understanding of the molecular mechanisms involved. That approach changed with the introduction of biologic therapeutics at the end of the 20th century and by the recent development of small-molecule inhibitors of intracellular signal transduction pathways. Here we compare and discuss the advantages and disadvantages of those two groups of targeted anti-inflammatory therapeutics.Discussion: TNF-blocking biologic agents were introduced into the therapy of rheumatoid arthritis and other autoimmune and inflammatory diseases in the late 1990s. Further biologic agents targeting cytokine networks or specific lymphocyte subsets have since been added to the armamentarium of anti-rheumatic therapy. During the last few years, another wave of novel discoveries led to the development of a new class of small molecule anti-inflammatory compounds targeting intracellular signal transduction molecules, such as tyrosine kinases. In all those cases, the specific targets of the drugs are well defined and significant knowledge about their role in the disease pathomechanism is available, qualifying them for being targeted therapeutics for inflammatory rheumatic diseases. While both groups of targeted therapeutics offer significant clinical benefit, they clearly differ in several aspects, such as the localization of their targets, their route of administration and target specificity, as well as technical details such as manufacturing procedures and cost basis. In this debate paper, we compare the advantages and disadvantages of the two different approaches, aiming to shed light on the possible future of targeted therapies.Summary: Biologic therapeutics and small-molecule inhibitors both have significant advantages and disadvantages in the therapy of rheumatic diseases. The future of targeted therapies is one of the most exciting questions of current rheumatology research and therapy. © 2014 Mócsai et al.; licensee BioMed Central Ltd
Prediction of the amount of secondary structure of proteins using unassigned NMR spectra: a tool for target selection in structural proteomics
Human and mouse essentiality screens as a resource for disease gene discovery.
The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery
A bi-objective optimization approach for configuring surgical trays with ergonomic risk consideration
Three new species of foliicolous Gomphillaceae (lichen-forming ascomycetes) from southern Florida
Home-Based Direct Care Workers
The objectives of the study were to profile occupational injury patterns across home health and hospice care (HHC), organization characteristics, and home health aides\u27 (HHAs) individual characteristics, and examine how worker training affects HHAs\u27 risk of reporting an injury using the model of human factors of health care in the home. The authors measured training knowledge using an 11-item scale and conducted univariate and bivariate analyses to describe injury patterns across individual, occupational, and organizational factors using STATA 12.0. The researchers found that work-related injuries and type of injury were associated with increased likelihood of reporting one or more injuries, full-time employment, high hourly pay, and working in an inpatient or mixed setting. Overall, HHAs perceived that they received excellent and good training on key topics that promoted safety and job knowledge. Furthermore, the results suggested linkages between worker\u27s complex personal, occupational, and organizational characteristics
- …