Project description:Behavioral analysis in preclinical neuropsychopharmacology relies on the accurate measurement of animal behavior. Several excellent solutions for computer-assisted behavioral analysis are available for specialized behavioral laboratories wishing to invest significant resources. Herein, we present an open source straightforward software solution aiming at the rapid and easy introduction to an experimental workflow, and at the improvement of training staff members in a better and more reproducible manual scoring of behavioral experiments with the use of visual aids-maps. Currently the program readily supports the Forced Swim Test, Novel Object Recognition test and the Elevated Plus maze test, but with minor modifications can be used for scoring virtually any behavioral test. Additional modules, with predefined templates and scoring parameters, are continuously added. Importantly, the prominent use of visual maps has been shown to improve, in a student-engaging manner, the training and auditing of scoring in behavioral rodent experiments.
Project description:Alternative splicing of mRNAs occurs in the majority of human genes, and most differential splicing results in different protein isoforms with possibly different functional properties. However, there are many reported splicing variations that may be quite rare, and not all combinatorially possible variants of a given gene are expressed at significant levels. Genes of interest to pharmacologists are frequently expressed at such low levels that they are not adequately represented in genome-wide studies of transcription. In single-gene studies, data are commonly available on the relative abundance and functional significance of individual alternatively spliced exons, but there are rarely data that quantitate the relative abundance of full-length transcripts and define which combinations of exons are significant. A number of criteria for judging the significance of splice variants and suggestions for their nomenclature are discussed.
Project description:BackgroundInternational medical graduates (IMGs) have significant exposure to clinical training in their home country, which provides opportunity for international comparison of training experiences. One relevant IMG population is Japanese physicians who have completed some training before entering residency programs in the United States and desire to improve medical education in Japan.ObjectiveWe examined Japanese IMGs' perceptions of the respective attributes of residency in the United States and Japan.MethodsIndividual semistructured interviews were conducted with 33 purposively sampled Japanese IMGs who had completed training. We used exploratory thematic analysis, iterative data collection, and thematic analyses with constant comparison.ResultsComments were organized into 3 categories: (1) attributes of US residency preferable to Japanese residency; (2) attributes of residency training with no clear preference for the US or Japanese systems; and (3) attributes of Japanese residency preferable to US residency. Within each category, we matched themes to residency program requirements or culture of medical training. Main themes include high regard for Accreditation Council for Graduate Medical Education (ACGME) Common Program Requirements, with emphasis on efficient achievement of clinical competency through graded responsibility, contrasted with preference expressed for a Japanese training culture of increased professional commitment facilitated by a lack of work hour limits and development of broad clinician skills, including bedside procedures and radiology interpretation.ConclusionsJapanese training culture contrasts with a US model that is increasingly focused on work-life balance and associated compartmentalization of patient care. These findings enhance our understanding of the global medical education landscape and challenges to international standardization of training.
Project description:ObjectiveTo determine the perspectives of Scottish accident and emergency (A&E) trainees and trainers on current training in the speciality, in order to help develop a simulator based training programme to complement existing training.MethodsQuestionnaires were sent to all Scottish A&E trainees and consultants responsible for training. They were presented with various clinical challenges. Trainees were asked to rate their confidence, experience, knowledge, and training on a Likert scale of 1 to 5. Trainers were asked to identify those areas where they felt trainees' performance consistently failed to meet a desired standard, and whether this was the result of lack of training, lack of exposure, or both.ResultsTrainees' response rate was 75%; consultants' was 59.4%. Overall trainees gave scores of 4/5 for confidence and knowledge, 3/5 for experience, and 2/5 for training. The highest scores were for medical, anaesthetics, and interpersonal skills. Consultants attributed lack of exposure to underperformance more frequently than lack of training.ConclusionsTrainees and trainers agree on the level of exposure to various clinical challenges, but disagree on training. Trainees' levels of confidence and knowledge outweigh their experience and training, suggesting that trainees associate knowledge with clinical competence.
Project description:The right to health as a fundamental human right is enshrined in the World Health Organization's charter and has been reaffirmed in international agreements spanning decades. This new journal reminds us of the essential characteristic of poverty as a violent abuse of human rights. The context of poverty - its social, political and economic dimensions - remain in the reader's mind as evidence is provided on technical solutions to managing the infectious diseases that afflict poor populations world-wide. Applying a health systems framework to a discussion on infectious diseases of poverty emerges from the papers in this journal's first edition. Many of the articles discuss treatments, indicating the importance of pharmaceuticals for neglected diseases. Delivery strategies to reach impoverished populations also figure within this first round of papers. Innovative programs that provide diagnostics and treatment for infectious diseases to hard-to-reach rural and urban communities are needed clearly needed, and some good examples are discussed here. Future editions will explore other health system components, broadening the evidence base to increase understanding of effective and sustainable interventions to reduce the burden of infectious disease among the poor. The editors are to be congratulated on the release of this inaugural issue of the journal Infectious Diseases of Poverty. We look forward to reading subsequent editions.
Project description:Here we present logic modeling as an approach to understand deregulation of signal transduction in disease and to characterize a drug's mode of action. We discuss how to build a logic model from the literature and experimental data and how to analyze the resulting model to obtain insights of relevance for systems pharmacology. Our workflow uses the free tools OmniPath (network reconstruction from the literature), CellNOpt (model fit to experimental data), MaBoSS (model analysis), and Cytoscape (visualization).
Project description:The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells.
Project description:Two technologies that have emerged in the last decade offer a new paradigm for modern pharmacology, as well as drug discovery and development. Quantitative systems pharmacology (QSP) is a complementary approach to traditional, target-centric pharmacology and drug discovery and is based on an iterative application of computational and systems biology methods with multiscale experimental methods, both of which include models of ADME-Tox and disease. QSP has emerged as a new approach due to the low efficiency of success in developing therapeutics based on the existing target-centric paradigm. Likewise, human microphysiology systems (MPS) are experimental models complementary to existing animal models and are based on the use of human primary cells, adult stem cells, and/or induced pluripotent stem cells (iPSCs) to mimic human tissues and organ functions/structures involved in disease and ADME-Tox. Human MPS experimental models have been developed to address the relatively low concordance of human disease and ADME-Tox with engineered, experimental animal models of disease. The integration of the QSP paradigm with the use of human MPS has the potential to enhance the process of drug discovery and development.
Project description:Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.
Project description:The European Trauma Course (ETC) exemplifies an innovative approach to multispecialty trauma education. This initiative was started as a collaborative effort among the European Society for Emergency Medicine, the European Society for Trauma and Emergency Surgery, and the European Society of Anaesthesiology under the auspices of the European Resuscitation Council. With the robust support of these societies, the project has evolved into the independent European Trauma Course Organisation. Over the past 15 years, the ETC has transcended traditional training by integrating team dynamics and non-technical skills into a scenario-based simulation course, helping to shape trauma care practice and education. A distinctive feature of the ETC is its training of doctors and allied healthcare professionals, fostering a collaborative and holistic approach to trauma care. The ETC stands out for its unique team-teaching approach, which has gained widespread recognition as the standard for in-hospital trauma care training not only in Europe but also beyond. Since its inception ETC has expanded geographically from Finland to Sudan and from Brazil to the Emirates, training nearly 20,000 healthcare professionals and shaping trauma care practice and education across 25 countries. Experiencing exponential growth, the ETC continues to evolve, reflecting its unmet demand in trauma team education. This review examines the evolution of the ETC, its innovative team-teaching methodology, national implementation strategies, current status, and future challenges. It highlights its impact on trauma care, team training, and the effect on other life support courses in various countries.