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The human endometrium is receptive to the embryo for a specific period of time known as the window of implantation (WOI). During this period, the endometrium shows a specific gene expression profile suitable for endometrial function evaluation. ER Map is a molecular tool able to accurately predict endometrial receptivity status by transcriptomic analysis. In this retrospective study, including 2256 subfertile patients undergoing ART treatment, the clinical value of precise WOI determination is studied in detail. Results obtained when single embryo transfers (sET) were scheduled either within the WOI timeframe as established by ER Map, or deviating from this WOI, are assessed and compared. Data obtained showed that 34.18% (771/2256) of patients had a displaced WOI. Analysis of ART outcomes showed significantly higher pregnancy rates in transfers scheduled within the WOI predicted compared to transfers that deviated more than 12h from this WOI (44.35% vs 23.08%, p

Despite recent advances, treatment of patients with aggressive Non-Hodgkin's lymphoma (NHL 2 ) has yet to be optimally designed. Notwithstanding the contribution of molecular treatments, intensiflcation of chemotherapeutic regimens may still be beneflcial. Hoping to aid in the design of intensifled chemotherapy, we put forward a mathematical and computational model that analyses the efiect of Doxorubicin on NHL over a wide range of patho-physiological conditions. The model represents tumour growth both in difiusion-limited settings, that is, in small avascular tumours and tumour cords, and in perfusion-limited settings, e.g. in well-vascularized tumours. Model simulations indicated the presence of a critical regimen intensity below which treatment will fall short of tumour elimination. Taking this critical intensity into account, we compared two regimen intensiflcation strategies: Dose escalation and regimen densiflcation, i.e. reducing the inter-dosing interval. In the difiusion-limited setting, dose escalation was somewhat more e-cient than regimen densiflcation. In the perfusion-limited setting, both intensiflcation strategies yielded similar results. The present study coupled with a realistic myelotoxicity model may add insight on the optimisation of NHL intensifled chemotherapy design.

International audience; Doxorubicin treatment outcomes for non-Hodgkin's lymphomas (NHL) are mathematically modelled and computationally analyzed. The NHL model includes a tumor structure incorporating mature and immature vessels, vascular structural adaptation and NHL cell-cycle kinetics in addition to Doxorubicin pharmacokinetics (PK) and pharmacodynamics (PD). Simulations provide qualitative estimations of the effect of Doxorubicin on high-grade (HG), intermediate-grade (IG) and low-grade (LG) NHL. Simulation results imply that if the interval between successive drug applications is prolonged beyond a certain point, treatment will be inefficient due to effects caused by heterogeneous blood flow in the system.

Background Improvements in the management of children with hepatoblastoma have followed advances made in cytotoxic agents and treatment regimens. The aim of this study was to quantify the effect of Lipiodol™, an iodinated poppy-seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in culture. Methods Monolayer cultures of (1) a hepatoblastoma cell line generated from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10 µg/ml with or without 2 per cent Lipiodol™ for 1–72 h. The fluorescence intensity in the treated cells, which correlates with intracellular doxorubicin concentration, was measured by confocal laser scanning microscopy. Cytotoxicity was assessed by trypan blue exclusion and electron microscopy. Results Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With Lipiodol™, the mean fluorescence intensity of intracellular doxorubicin was increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte cell line. Lipiodol™ increased the uptake and intracellular concentration of doxorubicin in the hepatoblastoma cells in culture. Lipiodol™ also enhanced the cytotoxicity of doxorubicin on the cultured hepatoblastoma cells. Conclusion Lipiodol™ significantly enhanced the uptake of doxorubicin by hepatoblastoma cells in culture. Lipiodol™–doxorubicin targeted treatment of hepatoblastoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling a reduction in the total dose administered and side-effects.

The Hybrid Cellular Automata (HCA) modelling framework can be an efficient approach to a number of biological problems, particularly those which involve the integration of multiple spatial and temporal scales. As such, HCA may become a key modelling tool in the development of the so-called integrative biology. In this paper, we first discuss HCA on a general level and then present results obtained when this approach was implemented in cancer research.

Background Limited information exists on the innervation of human cardiac valves and the relationship of nerve fibers and terminals with functional elements within leaflets. Methods and Results We examined human AV and arterial valves, obtained postmortem and at surgery, using quantitative immunohistochemical, histochemical, and confocal microscopic techniques. Significant differences in nerve density and distribution were found both between and within cardiac valves. Nerve density within the anterior leaflet of the mitral valve, for example, was twofold greater than that in the posterior leaflet ( P P Conclusions Human cardiac valves have distinct patterns of innervation that comprise both primary sensory and autonomic components. The presence of distinct nerve terminals and the close association of varicose nerve fibers with endothelial, smooth muscle, and fibroblast cells suggest a possible neural involvement in the control of valvar function.

The method for the separation of heavy petroleum hydrocarbons Into structural types-saturates, aromatics and polar materials has been modifled. The eluants, carbon tetrachloride and benzene that are carcinogenic and toxic, were successfully replaced with dichloromethane and petroleum spirit mixtures (35:65 and 82:18, respectively). The modified method was successfully applied to raffinates, extracts, hydrocracker products, heavy distillates, atmospheric and vacuum bottoms and other deasphalted residues (maltenes). An Improved handling technique was developed for hydrocarbon oils containing asphaltenes utilizing a preliminary deasphalting step with n-pentane. The precision of the technique was established for the saturates measured at ± 0.4% for a wide range of hydrocarbon oils.