Model-guided therapy for hepatocellular carcinoma: A role for information technology in predictive, preventive and personalized medicine

Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different disciplines including hepatologists, gastroenterologists, medical and surgical oncologists, liver transplant teams, interventional radiologists and radiation oncologists. The article concludes with a review providing an outlook and recommendations for the application of MGT to enhance the medical management of HCC through PPPM

Synthetic Sansanmycin Analogues as Potent Mycobacterium tuberculosis Translocase I Inhibitors.

Herein, we report the design and synthesis of inhibitors of Mycobacterium tuberculosis (Mtb) phospho-MurNAc-pentapeptide translocase I (MurX), the first membrane-associated step of peptidoglycan synthesis, leveraging the privileged structure of the sansanmycin family of uridylpeptide natural products. A number of analogues bearing hydrophobic amide modifications to the pseudo-peptidic end of the natural product scaffold were generated that exhibited nanomolar inhibitory activity against Mtb MurX and potent activity against Mtb in vitro. We show that a lead analogue bearing an appended neopentylamide moiety possesses rapid antimycobacterial effects with a profile similar to the frontline tuberculosis drug isoniazid. This molecule was also capable of inhibiting Mtb growth in macrophages where mycobacteria reside in vivo and reduced mycobacterial burden in an in vivo zebrafish model of tuberculosis

Germination capacity and viability of threatened species collections in seed banks

Facing the current biodiversity crisis, the value of ex situ conservation has been increasingly acknowledged in international treaties and legislations. Seed banks are a good way of conserving biodiversity, providing that seeds are of high quality and at maximum viability. However, despite the number of established ex situ facilities, there is little information on seed viability in botanic garden seed banks. This paper analyses the status of the seed collection of the National Botanic Garden of Belgium by determining the germination capacity and viability of seeds that have been stored for 1-26 years. It aims at: (1) ensuring that existing storage conditions provide effective ex situ conservation of threatened species; (2) providing viability data on threatened species; (3) planning future collection and storage efforts for seeds of West European species of conservation value. Results from this study showed that the germination and viability percentages of the 250 tested species reached on average 59 and 79% respectively. Some families typically performed better than others. Within a species, consistent results were not always obtained. Over a quarter of accessions exhibited some degree of dormancy. Considering the current lack of knowledge in seed germination and dormancy of many rare and threatened species, we believe that the quality of a seed collection should be estimated by its viability and not by its germination percentage. This study calls for further research in order to better understand the biology of a range of threatened native species. © Springer Science+Business Media B.V. 2009.SCOPUS: ar.jinfo:eu-repo/semantics/publishe