FARMAPRICE: A Pharmacogenetic Clinical decision support system for precise and Cost-Effective Therapy

Pharmacogenetic (PGx) guidelines for the precise dosing and selection of drugs remain poorly implemented in current clinical practice. Among the barriers to the implementation process is the lack of clinical decision support system (CDSS) tools to aid health providers in managing PGx information in the clinical context. The present study aimed to describe the first Italian endeavor to develop a PGx CDSS, called FARMAPRICE. FARMAPRICE prototype was conceived for integration of patient molecular data into the clinical prescription process in the Italian Centro di Riferimento Oncologico (CRO)-Aviano Hospital. It was developed through a coordinated partnership between two high-tech companies active in the computerization of the Italian healthcare system. Introducing FARMAPRICE into the clinical setting can aid physicians in prescribing the most efficacious and cost-effective pharmacological therapy available

Techno-Ecological Synergy: A Framework for Sustainable Engineering

Even though the importance of ecosystems in sustaining all human activities is well-known, methods for sustainable engineering fail to fully account for this role of nature. Most methods account for the demand for ecosystem services, but almost none account for the supply. Incomplete accounting of the very foundation of human well-being can result in perverse outcomes from decisions meant to enhance sustainability and lost opportunities for benefiting from the ability of nature to satisfy human needs in an economically and environmentally superior manner. This paper develops a framework for understanding and designing synergies between technological and ecological systems to encourage greater harmony between human activities and nature. This framework considers technological systems ranging from individual processes to supply chains and life cycles, along with corresponding ecological systems at multiple spatial scales ranging from local to global. The demand for specific ecosystem services is determined from information about emissions and resource use, while the supply is obtained from information about the capacity of relevant ecosystems. Metrics calculate the sustainability of individual ecosystem services at multiple spatial scales and help define necessary but not sufficient conditions for local and global sustainability. Efforts to reduce ecological overshoot encourage enhancement of life cycle efficiency, development of industrial symbiosis, innovative designs and policies, and ecological restoration, thus combining the best features of many existing methods. Opportunities for theoretical and applied research to make this framework practical are also discussed

Resveratrol in cancer patients: From bench to bedside

Resveratrol (3,5,4\u2032-trihydroxystilbene) is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients

Assessment of pharmacogenomic SLCO1B1 assay for prediction of neuromuscular pain in type 2 diabetes mellitus and cardiovascular patients: preliminary results

OBJECTIVE: At present, several strategies for preventing neuromuscular pain in Type 2 Diabetes Mellitus (T2DM) have been investigated. Recently, findings on genetic variants associated with adverse events to statin-based therapy have been reported. The study aimed at measuring whether Pharmacogenomics (PGx) profile can affect neuromuscular pain in patients carrying T2DM and cardiovascular diseases. An extensive panel of 5 polymorphisms on 4 candidate genes, previously validated as significant markers related to Sulphonylureas and Glitinides (SU-G) plus Simvastatin neuromuscular toxicity, is herein analyzed and discussed. PATIENTS AND METHODS: We genotyped 76 T2DM patients carrying cardiovascular dyscrasia undergone anti-diabetic and anti-cholesterolemic polypharmacy. 35 subjects out of the total received concurrent SU-G and Statin-based therapy. Candidate variants consisted of drug transporters, such as Solute Carrier Organic 1B1 (SLCO1B1) Val174Ala ATP-binding cassette subfamily B member (ABCB1), subfamily C member 8 (ABCC8), and drug biotransformers of Cytochrome P450 Family (CYP) including CYP2C9*2 CYP2C9*3 CYP2C8*3, and CYP3A4*22. Moreover, we also focused on an early outline evaluation of the genotyping costs and benefits. RESULTS: 6 out of 35 patients treated with SU-G plus statins (17.1% experienced adverse neuropathy events). Pharmacogenomics analysis showed a lack of any correlation between candidate gene polymorphisms and toxicity, except for the SLCO1B1 T521C allele; 14.3% of patients had a high risk for grade >2 neuromuscular pain (Odds Ratio [OR] 2.61.95% CI 0.90-7.61, p=0.03). CONCLUSIONS: The clinical polymorphism effectiveness outlined therein will be assured by diagnostic improvements suitable for driving treatment decisions. In light of our experimental results and literature data, the analysis of the SLCO1B1 T521C variant will allow clinicians to take advantage from a better treatment planned for their patients in order to minimize neuromuscular pain and maximize benefits