high-content-screening-analysis-to-evaluate-toxicological-effects

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)

Cigarette smoke (CS) is a major risk factor for cardiovascular and lung diseases. Because CS is a complex aerosol containing more than 7,000 chemicals1 it ...

Philip Morris International R&D

Immediate psychiatric care are realised either in the frame of acute traumatic crisis centres or on specific psychotraumatic consultations. They are indicated for victims of disasters, collective accidents, and hostages taken as well as for rescuers themselves, so frequently exposed to extreme situations. They are also indicated for victims of numerous individual aggressions who are seen in medico-judiciary emergencies. Their purpose is to reduce clinical manifestations of stress (adapted or complicated) by a quick intervention and to prevent the risk of installation of a chronic psychotraumatic syndrome, which is the principal psychiatric complication linked to these situations. These immediate psychiatric care allow the organisation of rapid psychotherapeutic interventions, i.e. psychological debriefing.

[Psychiatric care in emergency victims].

The distribution of pressure coefficient formed when the fluid contacts with the kayak oar blade is not been studied extensively. The CFD technique was employed to calculate pressure coefficient distribution on the front and rear faces of oar blade resulting from the numerical resolution equations of the flow around the oar blade in the steady flow conditions (4 m/s) for three angular orientations of the oar (45°, 90°, 135°) with main flow. A three-dimensional (3D) geometric model of oar blade was modeled and the k-ε turbulent model was applied to compute the flow around the oar. The main results reported that, under steady state flow conditions, the drag coefficient (Cd = 2.01 for 4 m/s) at 90° orientation has the similar evolution for the different oar blade orientation to the direction of the flow. This is valid when the orientation of the blade is perpendicular to the direction of the flow. Results indicated that the angle of oar strongly influenced the Cd with maximum values for 90° angle of the oar. Moreover, the distribution of the pressure is different for the internal and external edges depending upon oar angle. Finally, the difference of negative pressure coefficient Cp in the rear side and the positive Cp in the front side, contributes toward propulsive force. The results indicate that CFD can be considered an interesting new approach for pressure coefficient calculation on kayak oar blade. The CFD approach could be a useful tool to evaluate the effects of different blade designs on the oar forces and consequently on the boat propulsion contributing toward the design improvement in future oar models. The dependence of variation of pressure coefficient on the angular position of oar with respect to flow direction gives valuable dynamic information, which can be used during training for kayak competition.

The computational fluid dynamics study of orientation effects of oar-blade.

To identify the psychological repercussions of an error on professionals in intensive care and to understand their evolution. To identify the psychological defense mechanisms used by professionals to cope with error.

Error in intensive care: psychological repercussions and defense mechanisms among health professionals.

The purpose was to describe psychological experiences of patients 3 months after a stay in the intensive care unit (ICU) using qualitative methods.

Psychological experience of patients 3 months after a stay in the intensive care unit: A descriptive and qualitative study.

Cigarette smoke (CS) affects the adhesion of monocytes to endothelial cells, a critical step in atherogenesis. Using an in vitro adhesion assay together with innovative computational systems biology approaches to analyze omics data, our study aimed at investigating CS-induced mechanisms by which monocyte-endothelial cell adhesion is promoted. Primary human coronary artery endothelial cells (HCAECs) were treated for 4 h with (1) conditioned media of human monocytic Mono Mac-6 (MM6) cells preincubated with low or high concentrations of aqueous CS extract (sbPBS) from reference cigarette 3R4F for 2 h (indirect treatment, I), (2) unconditioned media similarly prepared without MM6 cells (direct treatment, D), or (3) freshly generated sbPBS (fresh direct treatment, FD). sbPBS promoted MM6 cells-HCAECs adhesion following I and FD, but not D. In I, the effect was mediated at a low concentration through activation of vascular inflammation processes promoted in HCAECs by a paracrine effect of the soluble mediators secreted by sbPBS-treated MM6 cells. Tumor necrosis factor α (TNFα), a major inducer, was actually shed by unstable CS compound-activated TNFα-converting enzyme. In FD, the effect was triggered at a high concentration that also induced some toxicity. This effect was mediated through an yet unknown mechanism associated with a stress damage response promoted in HCAECs by unstable CS compounds present in freshly generated sbPBS, which had decayed in D unconditioned media. Aqueous CS extract directly and indirectly promotes monocytic cell-endothelial cell adhesion in vitro via distinct concentration-dependent mechanisms.

Systems Biology Reveals Cigarette Smoke-Induced Concentration-Dependent Direct and Indirect Mechanisms That Promote Monocyte-Endothelial Cell Adhesion.

Alterations of endothelial adhesive properties by cigarette smoke (CS) can progressively favor the development of atherosclerosis which may cause cardiovascular disorders. Modified risk tobacco products (MRTPs) are tobacco products developed to reduce smoking-related risks. A systems biology/toxicology approach combined with a functional in vitro adhesion assay was used to assess the impact of a candidate heat-not-burn technology-based MRTP, Tobacco Heating System (THS) 2.2, on the adhesion of monocytic cells to human coronary arterial endothelial cells (HCAECs) compared with a reference cigarette (3R4F). HCAECs were treated for 4h with conditioned media of human monocytic Mono Mac 6 (MM6) cells preincubated with low or high concentrations of aqueous extracts from THS2.2 aerosol or 3R4F smoke for 2h (indirect treatment), unconditioned media (direct treatment), or fresh aqueous aerosol/smoke extracts (fresh direct treatment). Functional and molecular investigations revealed that aqueous 3R4F smoke extract promoted the adhesion of MM6 cells to HCAECs via distinct direct and indirect concentration-dependent mechanisms. Using the same approach, we identified significantly reduced effects of aqueous THS2.2 aerosol extract on MM6 cell-HCAEC adhesion, and reduced molecular changes in endothelial and monocytic cells. Ten- and 20-fold increased concentrations of aqueous THS2.2 aerosol extract were necessary to elicit similar effects to those measured with 3R4F in both fresh direct and indirect exposure modalities, respectively. Our systems toxicology study demonstrated reduced effects of an aqueous aerosol extract from the candidate MRTP, THS2.2, using the adhesion of monocytic cells to human coronary endothelial cells as a surrogate pathophysiologically relevant event in atherogenesis.

Systems toxicology-based assessment of the candidate modified risk tobacco product THS2.2 for the adhesion of monocytic cells to human coronary arterial endothelial cells.

Alexandra Laurent

Biological System Research (BSR)

Philip Morris International R&D

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)

Alexandra Laurent

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Biological System Research (BSR)

Philip Morris International R&D

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)

Biological System Research (BSR)