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The manifestation of metabolic deteriorations that accompany overweight and obesity can differ greatly between individuals, giving rise to a highly heterogeneous population. This inter-individual variation can impede both the provision and assessment of nutritional interventions as multiple aspects of metabolic health should be considered at once. Here, we apply the Mixed Meal Model, a physiology-based computational model, to characterize an individual's metabolic health in silico. A population of 342 personalized models were generated using data for individuals with overweight and obesity from three independent intervention studies, demonstrating a strong relationship between the model-derived metric of insulin resistance (ρ = 0.67, p < 0.05) and the gold-standard hyperinsulinemic-euglycemic clamp. The model is also shown to quantify liver fat accumulation and β-cell functionality. Moreover, we show that personalized Mixed Meal Models can be used to evaluate the impact of a dietary intervention on multiple aspects of metabolic health at the individual level., Competing Interests: D.M.J. and A.J.W. are employees of Unilever, which manufactures and markets consumer food products. L.S. is CEO and M.N. is in the scientific board of Caelus Pharmaceuticals, the Netherlands. However, these positions are not directly relevant for the content of this current paper. S.D.O’D., M.R., E.L.T., J.D.B., G.F., R.d.V., E.C.M.M., M.v.B., L.S., M.N., A.K.G., I.C.W.A., N.A.W.v.R., and L.A.A. declare no conflicts of interest., (© 2024 The Author(s).)

Recent developments in the understanding of the relationship between the microbiota and its host have provided evidence regarding the therapeutic potential of selected microorganisms to prevent or treat disease. According to Directive 2001/83/EC, in the European Union (EU), any product intended to prevent or treat disease is defined as a medicinal product and requires a marketing authorization by competent authorities prior to commercialization. Even if the pharmaceutical regulatory framework is harmonized at the EU level, obtaining marketing authorisations for medicinal products remains very challenging for Live Biotherapeutic Products (LBPs). Compared to other medicinal products currently on the market, safety assessment of LBPs represents a real challenge because of their specific characteristics and mode of action. Indeed, LBPs are not intended to reach the systemic circulation targeting distant organs, tissues, or receptors, but rather exert their effect through direct interactions with the complex native microbiota and/or the modulation of complex host-microbiota relation, indirectly leading to distant biological effects within the host. Hence, developers must rely on a thorough risk analysis, and pharmaceutical guidelines for other biological products should be taken into account in order to design relevant non-clinical and clinical development programmes. Here we aim at providing a roadmap for a risk analysis that takes into account the specificities of LBPs. We describe the different risks associated with these products and their interactions with the patient. Then, from that risk assessment, we propose solutions to design non-clinical programmes and First in Human (FIH) early clinical trials appropriate to assess LBP safety., (Copyright © 2020 Rouanet, Bolca, Bru, Claes, Cvejic, Girgis, Harper, Lavergne, Mathys, Pane, Pot, Shortt, Alkema, Bezulowsky, Blanquet-Diot, Chassard, Claus, Hadida, Hemmingsen, Jeune, Lindman, Midzi, Mogna, Movitz, Nasir, Oberreither, Seegers, Sterkman, Valo, Vieville and Cordaillat-Simmons.)

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled 'Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies'. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation-health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation-health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

Recently, it was shown that aspirin given early in acute myocardial infarction (AMI) improves hospital survival, but the mechanisms involved are unclear. In a prospective, randomized placebo-controlled trial, the influence of early intervention with low-dose aspirin (100 mg/day) on infarct size and clinical outcome was studied in 100 consecutive patients with first anterior wall AMI. Infarct size was calculated by cumulative lactate dehydrogenase release in the first 72 hours after admission and was found to be (mean +/- standard deviation) 1,431 +/- 782 U/liter in the aspirin group (n = 50) and 1,592 +/- 1,082 U/liter in the placebo group (n = 50, p = 0.35). The study medication was given for 3 months, during which mortality was 10 (20%) in the aspirin patients and 12 (24%) in the placebo patients (p = 0.65). However, reinfarction occurred in 2 patients (4%) in the aspirin group and in 9 (18%) in the placebo group (p less than 0.03). Early intervention with low-dose aspirin showed, in comparison to placebo, a 10% decrease of infarct size, but this difference was not statistically significant. However, early low-dose aspirin effectively decreased the risk of reinfarction. Therefore, the favor able results of early aspirin on mortality in acute myocardial infarction are probably due more to prevention of reinfarction than to decrease of infarct size.

Between September 1, 1986, and December 31, 1987, sixty-four consecutive patients younger than 70 years, with early (less than 4 hours) symptoms and signs of myocardial infarction, were treated with 1.5 million units streptokinase intravenously in the emergency room (ER group) before admission to the coronary care unit. Data from these patients were compared in retrospect to those of 66 consecutive patients with myocardial infarction who were treated with intravenous streptokinase in the coronary care unit (CCU group) before September 1, 1986. Time between first symptoms and initiation of fibrinolytic therapy was significantly shorter in the ER group: 114 +/- 53 minutes vs 150 +/- 56 minutes in the CCU group (p less than 0.001). The incidence of in-hospital complications was similar in both groups. However, left ventricular stroke work index during the stay in the coronary care unit was 50 +/- 19 gm/m2 in the ER group vs 42 +/- 14 in the CCU group (p = 0.02). Also the echocardiographic left ventricular wall motion score at 48 hours after admission tended to be better in the ER group: 6.7 +/- 4.0 compared to that in the CCU group (7.6 +/- 4.5; p = 0.29). In conclusion, infusion of intravenous streptokinase in the emergency room is feasible and safe and results in a significant time gain leading to a better hemodynamic profile. Within the hospital the emergency room is the ideal place for intravenous fibrinolytic therapy in eligible patients with acute myocardial infarction.