Title Participants Abstract "A Multi-method Approach towards Understanding the Pathophysiology of Aortic Dissections - The Complementary Role of In-Silico, In-Vitro and In-Vivo Information" "Bart Bijnens" "Management and follow-up of chronic aortic dissections continues to be a clinical challenge due to progressive aortic dilatation. To predict dilatation, guidelines suggest follow-up of the aortic diameter. However, dilatation is triggered by haemodynamic parameters (pressure and wall shear stresses (WSS)), and geometry of false (FL) and true lumen (TL). We aimed at a better understanding of TL and FL haemodynamics by performing in-silico (CFD) and in-vitro studies on an idealized dissected aorta and compared this to a typical patient. We observed an increase in diastolic pressure and wall stress in the FL and the presence of diastolic retrograde flow. The inflow jet increased WSS at the proximal FL while a large variability in WSS was induced distally, all being risk factors for wall weakening. In-silico, in-vitro and in-vivo findings were very similar and complementary, showing that their combination can help in a more integrated and extensive assessment of aortic dissections, improving understanding of the haemodynamic conditions and related clinical evolution. © 2010 Springer-Verlag Berlin Heidelberg." "In-vitro and in-vivo evaluation of the modulatory effects of the multitarget compound ASS234 on the monoaminergic system" "Gerard Esteban, Jolien Van Schoors, Ping Sun, Ann Van Eeckhaut, José Marco-Contelles, Ilse Smolders, Mercedes Unzeta" "OBJECTIVES: To evaluate the in-vitro and in-vivo effects on monoaminergic neurotransmission of ASS234, a promising multitarget-directed ligand (MTDL), for Alzheimer's disease (AD) therapy.METHODS: In vitro was explored the effect of ASS234 on the monoaminergic metabolism in SH-SY5Y and PC12 cell lines, and remaining activity of both monoamine oxidase (MAO) isoforms was assessed. The corresponding dopamine (DA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) and noradrenaline (NA) levels were determined by HPLC-ED. In-vivo experiments were carried out Wistar rats and intracerebral guide cannulas were implanted in the hippocampus and in the prefrontal cortex by sterotaxic coordinates. The day after microdialysis samples were collected and levels of 5-HT, DA and NA were determined by (UHPLC) with electrochemical detector.KEY FINDINGS: ASS234 induced a significant increase in serotonin (5-HT) levels in SH-SY5Y cells. In PC12 cells, ASS234 increased significantly the ratio of dopamine (DA)/(HVA + DOPAC), although no apparent differences in (NA) were observed. By in-vivo microdialysis, ASS234 showed a significant increase in the extracellular levels of 5-HT and NA in hippocampus whereas in the prefrontal cortex, DA and NA also increased significantly.CONCLUSIONS: This study reveals the ability of ASS234 a MTDL compound, to enhance the monoaminergic neurotransmission supporting its potential use in AD therapy." "The impact of force-degraded variants of recombinant human follicle stimulating hormone alfa (r-hFSH alfa) on in-vitro and in-vivo biological activity" "Thomas D'Hooghe" "Uncoupling of in-vitro identity of embryonic limb derived skeletal progenitors and their in-vivo bone forming potential" "Louca Verbeeck, Liesbet Geris, Przemko Tylzanowski, Frank Luyten" "The healing of large bone defects remains a major unmet medical need. Our developmental engineering approach consists of the in vitro manufacturing of a living cartilage tissue construct that upon implantation forms bone by recapitulating an endochondral ossification process. Key to this strategy is the identification of the cells to produce such cartilage intermediates efficiently. We applied a cell selection strategy based on published skeletal stem cell markers using mouse embryonic limb cartilage as cell source and analysed their potential to form bone in an in vivo ectopic assay. FGF2 supplementation to the culture media for expansion blocked dedifferentiation of the embryonic cartilage cells in culture and enriched for stem cells and progenitors as quantified using the recently published CD marker set. However, when the stem cells and progenitors were fractionated from expanded embryonic cartilage cells and assessed in the ectopic assay, a major loss of bone forming potential was observed. We conclude that cell expansion appears to affect the association between cell identity based on CD markers and in vivo bone forming capacity." "In-Vivo, In-Vitro and In-Silico methods for Small Molecule transfer across the BBB" "Patrick Augustijns" "The inability of molecules to permeate the BBB is a significant source of attrition in Central Nervous System (CNS) drug discovery. Given the increasing medical drivers for new and improved CNS drugs, small molecule transfer across the BBB is attracting a heightened awareness within pharmaceutical industry and medical fields. In order to assess the potential for small CNS molecules to permeate the BBB, a variety of methods and models, from in silico to in vivo going through in vitro models are developed as predictive tools in drug discovery. This review gives a comprehensive overview of different approaches currently considered in drug discovery to circumvent the lack of small molecule transfer through the BBB, together with their inherent advantages and disadvantages. Particularly, special attention is drawn to in silico models, with a detailed and contemporary point of view on prediction tools and guidelines for rational design." "In-vitro and in-vivo evaluation of enteric-coated starch-based pellets prepared via extrusion/spheronisation" "A DUKIC-OTT, Thomas De Beer, Jean Paul Remon, Willy Baeyens, P FOREMAN, Chris Vervaet" "In-vitro and in-vivo evidence for the anti-inflammatory activity of hop bitter acids in mouse" "Marjan Van Cleemput, Arne Heyerick, Claude Libert, Denis De Keukeleire, Guy Haegeman, Karolien De Bosscher" "In-vitro maturation of oocytes versus conventional IVF in women with infertility and a high antral follicle count" "Thi Ngoc Lan Vuong, Ngoc Anh Vu Ho, Manh Tuong Ho, Vinh Q Dang, Tuan H Phung, Nhu H Giang, Anh Hoang Le Tuan, Toan D Pham, Rui Wang, Johan Smitz, Robert B Gilchrist, Robert J. Norman, Ben Willem J Mol" "STUDY QUESTION: Is one cycle of IVM non-inferior to one cycle of conventional in IVF with respect to live birth rates in women with high antral follicle counts (AFCs)?SUMMARY ANSWER: We could not demonstrate non-inferiority of IVM compared with IVF.WHAT IS KNOWN ALREADY: IVF with ovarian hyperstimulation has limitations in some subgroups of women at high risk of ovarian stimulation, such as those with polycystic ovary syndrome. IVM is an alternative ART for these women. IVM may be a feasible alternative to IVF in women with a high AFC, but there is a lack of data from randomized clinical trials comparing IVM with IVF in women at high risk of ovarian hyperstimulation syndrome.STUDY DESIGN, SIZE, DURATION: This single-center, randomized, controlled non-inferiority trial was conducted at an academic infertility center in Vietnam from January 2018 to April 2019.PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 546 women with an indication for ART and a high AFC (≥24 follicles in both ovaries) were randomized to the IVM (n = 273) group or the IVF (n = 273) group; each underwent one cycle of IVM with a prematuration step versus one cycle of IVF using a standard gonadotropin-releasing hormone antagonist protocol with gonadotropin-releasing hormone agonist triggering. The primary endpoint was live birth rate after the first embryo transfer. The non-inferiority margin for IVM versus IVF was -10%.MAIN RESULTS AND THE ROLE OF CHANCE: Live birth after the first embryo transfer occurred in 96 women (35.2%) in the IVM group and 118 women (43.2%) in the IVF group (absolute risk difference -8.1%; 95% confidence interval (CI) -16.6%, 0.5%). Cumulative ongoing pregnancy rates at 12 months after randomization were 44.0% in the IVM group and 62.6% in the IVF group (absolute risk difference -18.7%; 95% CI -27.3%, -10.1%). Ovarian hyperstimulation syndrome did not occur in the IVM group, versus two cases in the IVF group. There were no statistically significant differences between the IVM and IVF groups with respect to the occurrence of pregnancy complications, obstetric and perinatal complications, preterm delivery, birth weight and neonatal complications.LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study was its open-label design. In addition, the findings are only applicable to IVM conducted using the prematuration step protocol used in this study. Finally, the single ethnicity population limits the external generalizability of the findings.WIDER IMPLICATIONS OF THE FINDINGS: Our randomized clinical trial compares live birth rates after IVM and IVF. Although IVM is a viable and safe alternative to IVF that may be suitable for some women seeking a mild ART approach, the current study findings approach inferiority for IVM compared with IVF when cumulative outcomes are considered. Future research should incorporate multiple cycles of IVM in the study design to estimate cumulative fertility outcomes and better inform clinical decision-making.STUDY FUNDING/COMPETING INTEREST(S): This work was partly supported by Ferring grant number 000323 and funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) and by the Fund for Research Flanders (FWO). LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; RJN has received conference and scientific board fees from Ferring, is a minor shareholder in an IVF company, and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant; RBG reports grants and fellowships from the NHMRC of Australia; JS reports lecture fees from Ferring Pharmaceuticals, Biomérieux, Besins Female Healthcare and Merck, grants from Fund for Research Flanders (FWO), and is co-inventor on granted patents on CAPA-IVM methodology in the US (US10392601B2) and Europe (EP3234112B1); TDP, VQD, VNAH, NHG, AHL, THP and RW have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.TRIAL REGISTRATION NUMBER: NCT03405701 (www.clinicaltrials.gov).TRIAL REGISTRATION DATE: 16 January 2018.DATE OF FIRST PATENT’S ENROLMENT: 25 January 2018." "Inertial control: a novel technique for in-vitro analysis of foot function" "Tassos Natsakis, Koen Peeters, Fien Burg, Greta Dereymaeker, Jos Vander Sloten, Ilse Jonkers" "Background In-vitro gait simulations have great potential, allowing a systematic analysis of the foot function. However, it is important that the loading conditions are realistic i.e. physiologic ground reaction forces (GRF). In most experiments, in-vivo measured GRF can be imposed [1, 2]. However in experimental designs that evaluate the effect of altered muscle forces on foot motion this is more complex; the effect of the altered muscle activity on the loading and kinematics cannot be taken into consideration. Therefore, we investigated the use of a new technique to simulate such cases with realistic loading conditions. Methods Our gait simulator simulates the activation of nine muscles (grouped in six groups), based on electromyography measurements. The forces are applied with pneumatic actuators and are measured by load-cells located between the tendons and the actuators. The set-up is able to simulate knee motion, using a motor for the horizontal and a platform under the foot for the vertical direction. The stance phase is simulated in 0.8 seconds. The GRF in human gait is the sum of a static (human weight) and a dynamic part (acceleration of human mass). By applying a constant force on the platform (equal to the assumed weight of the subject), the measured GRF is the sum of the constant force and the force generated from the acceleration of the platform. This way, the kinetics are governed exclusively by the muscle activation. Results Four freshly frozen cadaveric specimens were used, for five measurements each. The in-vitro measured GRF was compared to in-vivo measurements (figure 1) and followed the normal pattern with an RMS error of 22%. Conclusions Using this method, physiological GRF were reconstructed for normal gait, by reconstructing the mechanism that generates GRF. It could be, therefore, used for pathologic gait simulations, since the mechanism is identical." "Recovery and in-vitro culture of early preantral guinea pig follicles" "Iris Adriaens, Clair SADEU DONGFACK Jean, Paul Jacquet" "The guinea pig oocyte is a better model than the mouse oocyte for studies on genetic hazard of ionizing radiation on the human female gamete. Confrontation with the several limitations of in-vivo studies, incited to work on the development of an in-vitro system for guinea pig ovarian follicles. This manuscript describes the isolation of intact preantral guinea pig follicles and their subsequent stepwise culture development. Intact early preantral follicles can be grown up to the late preantral/early antral follicle stage within a culture period of 21 days. Steroid production patterns in conditioned medium prove the functionality of the theca-granulosa interaction. An ovulatory stimulus can reinitiate oocyte maturation. Current setup allows to culture oocytes that reach 86.5% of the final maximal diameter of in-vivo grown oocytes and proceed to GVBD in 80%. In order to obtain fully matured MII oocytes a further final step in the culture system is needed."