Evidence based medicine: an approach to clinical problem-solving.

Doctors within the NHS are confronting major changes at work. While we endeavour to improve the quality of health care, junior doctors'' hours have been reduced and the emphasis on continuing medical education has increased. We are confronted by a growing body of information, much of it invalid or irrelevant to clinical practice. This article discusses evidence based medicine, a process of turning clinical problems into questions and then systematically locating, appraising, and using contemporaneous research findings as the basis for clinical decisions. The computerisation of bibliographies and the development of software that permits the rapid location of relevant evidence have made it easier for busy clinicians to make best use of the published literature. Critical appraisal can be used to determine the validity and applicability of the evidence, which is then used to inform clinical decisions. Evidence based medicine can be taught to, and practised by, clinicians at all levels of seniority and can be used to close the gulf between good clinical research and clinical practice. In addition it can help to promote self directed learning and teamwork and produce faster and better doctors.     

GOTreePlus: an interactive gene ontology browser

Summary: We developed an interactive gene ontology (GO) browsernamed GOTreePlus that superimposes annotation information overGO structures. It can facilitate the identification of importantGO terms through interactive visualization of them in the GOstructure. The interactive pie chart summarizing an annotationdistribution for a selected GO term provides users with a succinctcontext-sensitive overview of their experimental results. Wetested our GOTreePlus using a proteome profiling dataset obtainedon differentiation of retinal pigment epithelial cells where399 proteins were quantified. Availability: http://bioinformatics.cnmcresearch.org/GOTreePlus/ Contact: jseo{at}cnmcresearch.org Associate Editor: John Quackenbush     

Preparing physicians to utilize the emerging genetic toolbox: an approach for medical biochemistry

New genetic information is accumulating so rapidly that even the most current material given to first or second year medical students about any specific genetic disease may be incomplete if not obsolete before they obtain the M.D. degree. Therefore, medical education must emphasize the principles of molecular biology and genetics while providing students with the skills to independently obtain up-to-date genetic information following graduation. An assignment that requires students to acquire details about a particular genetic disease from various on-line resources is one method being used to accomplish the latter goal.     

Network medicine: a network-based approach to human disease

Given the functional interdependencies between the molecular components in a human cell, a disease is rarely a consequence of an abnormality in a single gene, but reflects the perturbations of the complex intracellular and intercellular network that links tissue and organ systems. The emerging tools of network medicine offer a platform to explore systematically not only the molecular complexity of a particular disease, leading to the identification of disease modules and pathways, but also the molecular relationships among apparently distinct (patho)phenotypes. Advances in this direction are essential for identifying new disease genes, for uncovering the biological significance of disease-associated mutations identified by genome-wide association studies and full-genome sequencing, and for identifying drug targets and biomarkers for complex diseases.     

Gallstones - approach to medical management

Between 10% and 15% of individuals in the industrialized world have gallstones. The standard treatment is laparoscopic cholecystectomy, making gallstone disease the second most costly digestive disorder in most Western countries. Despite a rapid convalescence, the procedure is not devoid of morbidity or even mortality. Bile duct injury is particularly troublesome, occurring in 0.1% to 0.5% of cases, even in the most experienced hands. Moreover, some 20% of patients continue to suffer from pain (the main indication for treatment) after cholecystectomy. In patients with mild symptoms, surgical treatment has been associated with a higher morbidity than the natural course of the disease. Medical dissolution therapy with bile acids is an alternative for patients with mild-to-moderate symptoms due to cholesterol gallstones. Chenodeoxycholic acid (CDCA, chenodiol) has been largely replaced by the safer and more efficient ursodeoxycholic acid (UDCA). The main drawbacks of UDCA treatment are its low efficacy (approximately 40%), slowness in action, and the possibility of stone recurrence. However, this treatment is extremely safe, and the efficacy and slowness can be somewhat improved by stricter patient selection. Moreover, patient symptoms may respond to this therapy even without complete stone dissolution. New strategies employing more efficient bile acids or related compounds may increase the efficacy of medical dissolution. Furthermore, recent advances in the understanding of biliary lipid secretion and regulation should offer novel opportunities to further improve the prospects of medical treatment of gallstones.     

A network medicine approach to human disease

High-throughput interaction discovery initiatives are providing thousands of novel protein interactions which are unveiling many unexpected links between apparently unrelated biological processes. In particular, analyses of the first draft human interactomes highlight a strong association between protein network connectivity and disease. Indeed, recent exciting studies have exploited the information contained within protein networks to disclose some of the molecular mechanisms underlying complex pathological processes. These findings suggest that both protein-protein interactions and the networks themselves could emerge as a new class of targetable entities, boosting the quest for novel therapeutic strategies.     

Development of FuGO: an ontology for functional genomics investigations

The development of the Functional Genomics Investigation Ontology (FuGO) is a collaborative, international effort that will provide a resource for annotating functional genomics investigations, including the study design, protocols and instrumentation used, the data generated and the types of analysis performed on the data. FuGO will contain both terms that are universal to all functional genomics investigations and those that are domain specific. In this way, the ontology will serve as the "semantic glue" to provide a common understanding of data from across these disparate data sources. In addition, FuGO will reference out to existing mature ontologies to avoid the need to duplicate these resources, and will do so in such a way as to enable their ease of use in annotation. This project is in the early stages of development; the paper will describe efforts to initiate the project, the scope and organization of the project, the work accomplished to date, and the challenges encountered, as well as future plans.