Conductance-Based Adaptive Exponential Integrate-and-Fire Model.

The intrinsic electrophysiological properties of single neurons can be described by a broad spectrum of models, from realistic Hodgkin-Huxley-type models with numerous detailed mechanisms to the phenomenological models. The adaptive exponential integrate-and-fire (AdEx) model has emerged as a convenient middle-ground model. With a low computational cost but keeping biophysical interpretation of the parameters, it has been extensively used for simulations of large neural networks. However, because of its current-based adaptation, it can generate unrealistic behaviors. We show the limitations of the AdEx model, and to avoid them, we introduce the conductance-based adaptive exponential integrate-and-fire model (CAdEx). We give an analysis of the dynamics of the CAdEx model and show the variety of firing patterns it can produce. We propose the CAdEx model as a richer alternative to perform network simulations with simplified models reproducing neuronal intrinsic properties.

Dendritic sodium spikes endow neurons with inverse firing rate response to correlated synaptic activity.

Many neurons possess dendrites enriched with sodium channels and are capable of generating action potentials. However, the role of dendritic sodium spikes remain unclear. Here, we study computational models of neurons to investigate the functional effects of dendritic spikes. In agreement with previous studies, we found that point neurons or neurons with passive dendrites increase their somatic firing rate in response to the correlation of synaptic bombardment for a wide range of input conditions, i.e. input firing rates, synaptic conductances, or refractory periods. However, neurons with active dendrites show the opposite behavior: for a wide range of conditions the firing rate decreases as a function of correlation. We found this property in three types of models of dendritic excitability: a Hodgkin-Huxley model of dendritic spikes, a model with integrate and fire dendrites, and a discrete-state dendritic model. We conclude that fast dendritic spikes confer much broader computational properties to neurons, sometimes opposite to that of point neurons.

Effects of Rivaroxaban Therapy on ROTEM Coagulation Parameters in Patients with Venous Thromboembolism.

BACKGROUND: Rivaroxaban (Xarelto) does not require routine coagulation monitoring; however, in certain clinical situations (overdose, drug accumulation, urgent surgery) measurement of its plasma concentration is highly recommended. Currently, there is no single hemostasis test that shows a direct correlation between rivaroxaban plasma levels and anticoagulant efficacy. OBJECTIVES: This study was intended to assess the value of ROTEM in determining rivaroxaban administration. MATERIAL AND METHODS: Thirteen patients with venous thromboembolism and 13 healthy volunteers were compared with regard to certain ROTEM parameters and anti-FXa activity. The tests were done before the administration of 20 mg rivaroxaban (i.e. 24 h after previous administration) and 2.5 h afterwards. RESULTS: The study group demonstrated residual activity of rivaroxaban in plasma (20 ± 11.3 ng/mL) 24 h following the previous administration, which did not cause marked changes in clotting assays compared to controls. In the group, 2.5 h after rivaroxaban administration, prolongation of PT (PTratio 1.51 ± 0.22), APTT (APPTratio: 1.30 ± 0.14) and ROTEM CT (CTratio - EXTEM: 2.45 ± 1.06, CTratio - INTEM: 1.32 ± 0.21) were observed. The cut-off values for particular tests were created to determine if the patient had achieved desirable anticoagulant effect after rivaroxaban administration. The mean anti-FXa values were significantly lower in patients before rivaroxaban dosing than after. CONCLUSIONS: PT demonstrated better diagnostic value than APTT in rivaroxaban administration. The ROTEM clotting time (CT) according to EXTEM may be used to determine the anticoagulation effect of rivaroxaban, but is not sensitive enough to measure the residual activity of this drug.

Evaluation of an injectable, photopolymerizable, and three-dimensional scaffold based on methacrylate-endcapped poly(D,L-lactide-co-epsilon-caprolactone) combined with autologous mesenchymal stem cells in a goat tibial unicortical defect model.

An in situ crosslinkable, biodegradable, methacrylate-endcapped poly(D,L-lactide-co-epsilon-caprolactone) in which crosslinkage is achieved by photoinitiators was developed for bone tissue regeneration. Different combinations of the polymer with bone marrow-derived mesenchymal stem cells (BMSCs) and alpha-tricalcium phosphate (alpha-TCP) were tested in a unicortical tibial defect model in eight goats. The polymers were randomly applied in one of three defects (6.0 mm diameter) using a fourth unfilled defect as control. Biocompatibility and bone-healing characteristics were evaluated by serial radiographies, histology, histomorphometry, and immunohistochemistry. The results demonstrated cell survival and proliferation in the polymer-substituted bone defects. The addition of alpha-TCP was associated with less expansion and growth of the BMSCs than other polymer composites.

Immediate postextraction implant placement in sheep's mandibles: a pilot study.

PURPOSE: In this study, sheep were examined as a potential animal model for immediate implant placement in fresh extraction sockets using experimental photopolymerisable bioabsorbable polymers. MATERIALS: A total of 22 cylindrical implants were placed in fresh mandibular premolar extraction sockets of 7 sheep. Residual bone-implant voids were filled with a biocompatible composite of poly-methyl-methacrylate and poly-hydroxyl-ethyl-methacrylate (Bioplant 24). Photopolymerisation of a viscose mixture of experimental prepolymers and Bioplant 24 applied to the neck of the implants provided additional support before gingival closure. Clinical and radiographic controls were performed 30, 90, and 180 days after surgery. At 180 days postoperatively, the sheep were sacrificed and the mandibular segments were isolated for histological processing. RESULTS: High cumulative implant failure rates of 45.5%, 63.6%, and 77.3% at respectively 30, 90 and 180 days were recorded. Significantly more implants were lost when the position of the neck was located above the level of the alveolar crest (P < 0.05). Clinical and histological observations demonstrated poor implant osseointegration characterized by ingrowth of soft tissue into the extraction sockets. Bone substitutes were lost in all cases. DISCUSSION AND CONCLUSION: Sheep have many practical advantages compared with other animal models. However, their specific oral biomechanics inherent to their constant ruminant activity accounted for a high degree of the reported implant failures. Important adaptations to the implantation technique and postoperative management will be necessary to use sheep as an animal model for future oral implant related experiments.

Encapsulation of osteoblast seeded microcarriers into injectable, photopolymerizable three-dimensional scaffolds based on d,l-lactide and epsilon-caprolactone.

UMR-106 seeded microcarriers were encapsulated into in situ, photopolymerizable three-dimensional scaffolds based on d,l-lactide and epsilon-caprolactone. UMR-106 and rat bone marrow cells proliferated and differentiated well on the microcarriers. The microcarriers were completely colonized after 14 days in culture. The viscous polymer paste allowed to mix the UMR-106 seeded microcarriers and gelatin (porosigen) properly. After the photopolymerization process, microcarriers and gelatin were evenly distributed throughout the scaffold. Gelatin was leached out within 7 h, and a porous scaffold was obtained. The microcarriers remained in the scaffold even after 7 days which demonstrates that they were well entrapped in the polymer. Increasing the amount of entrapped microcarriers (20-50%) leads to scaffolds with a reduced cross-linking. Hence, the microcarriers leached out. The encapsulated UMR-106 cells did not show pyknotic nuclei which demonstrates that the photopolymerization and handling the viscous polymer/gelatin/microcarrier paste is not detrimental for the cells.