Inhibition of the dorsolateral cortex reveals specific mechanisms behind emotional control.

Reappraisal is a complex emotional control strategy based on cognitive change. To complete the reappraisal task, one is required to deeply elaborate on the affective stimulus to create its new interpretation. The involvement of the prefrontal cortex in this process was examined in the study, where inhibition of the left or right dorsolateral area was carried out using transcranial magnetic stimulation. In a between-subject design, we used an alternative control condition for the reappraisal task. It was intended to better account for overall task activity compared to typical passive conditions. Late positive potential was affected after inhibition of the prefrontal area, suggesting hindered emotional control. This effect was specific to the reappraisal task, which possibly reflects the disturbance of attention allocation to emotional stimuli. We could also observe an increased transfer of information from the visual area during the control task that was based on the elaboration of emotional stimuli but did not involve cognitive change. Our results support the additive impact of several factors on the overall efficiency of emotional control.

Continuous Delivery of Blockchain Distributed Applications.

Ensuring a production-ready state of the application under development is the imminent feature of the Continuous Delivery (CD) approach. In a blockchain network, nodes communicate and store data in a distributed manner. Each node executes the same business application but operates in a distinct execution environment. The literature lacks research focusing on continuous practices for blockchain and Distributed Ledger Technology (DLT). Specifically, it lacks such works with support for both design and deployment. The author has proposed a solution that takes into account the continuous delivery of a business application to diverse deployment environments in the DLT network. As a result, two continuous delivery pipelines have been implemented using the Jenkins automation server. The first pipeline prepares a business application whereas the second one generates complete node deployment packages. As a result, the framework ensures the deployment package in the actual version of the business application with the node-specific up-to-date version of deployment configuration files. The Smart Contract Design Pattern has been used when building a business application. The modeling aspect of blockchain network installation has required using Unified Modeling Language (UML) and the UML Profile for Distributed Ledger Deployment. The refined model-to-code transformation generates deployment configurations for nodes. Both the business application and deployment configurations are stored in the GitHub repositories. For the sake of verification, tests have been conducted for the electricity consumption and supply management system designed for prosumers of renewable energy.

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.

Cholinergic Switch between Two Types of Slow Waves in Cerebral Cortex.

Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory versus excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.

Bridging Single Neuron Dynamics to Global Brain States.

Biological neural networks produce information backgrounds of multi-scale spontaneous activity that become more complex in brain states displaying higher capacities for cognition, for instance, attentive awake versus asleep or anesthetized states. Here, we review brain state-dependent mechanisms spanning ion channel currents (microscale) to the dynamics of brain-wide, distributed, transient functional assemblies (macroscale). Not unlike how microscopic interactions between molecules underlie structures formed in macroscopic states of matter, using statistical physics, the dynamics of microscopic neural phenomena can be linked to macroscopic brain dynamics through mesoscopic scales. Beyond spontaneous dynamics, it is observed that stimuli evoke collapses of complexity, most remarkable over high dimensional, asynchronous, irregular background dynamics during consciousness. In contrast, complexity may not be further collapsed beyond synchrony and regularity characteristic of unconscious spontaneous activity. We propose that increased dimensionality of spontaneous dynamics during conscious states supports responsiveness, enhancing neural networks' emergent capacity to robustly encode information over multiple scales.

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.

Osteoblast behaviour on in situ photopolymerizable three-dimensional scaffolds based on D,L-lactide and epsilon-caprolactone: influence of pore volume, pore size and pore shape.

Bone marrow cells were cultured on in situ photopolymerizable scaffolds based on D,L-lactide and epsilon-caprolactone. The influence of pore volume, size and shape were evaluated. Bone formation was demonstrated by ALP activity, osteocalcin secretion and histological analysis. TEM at the polymer interface revealed osteoblasts which secreted an extracellular matrix containing matrix vesicles loaded with apatite. Cellular infiltration was possible for scaffolds with a porosity of 70 and gelatin particle size of 250-355 microm. Scaffolds with a porosity less than 70 had the tendency to form a polymer top layer. Although increasing the gelatin particle size to 355-500 microm, leads to infiltration even in scaffolds with a porosity of 60. No infiltration was possible in scaffolds with sodium chloride as porogen. On the contrary, sucrose and gelatin leads to better interconnected scaffolds at the same porosity. Hence, spherical gelatin particles are suitable to use as porogen in photopolymerizable scaffolds.

Evaluation of an injectable, photopolymerizable three-dimensional scaffold based on D: ,L: -lactide and epsilon-caprolactone in a tibial goat model.

An in situ crosslinkable, biodegradable, methacrylate-encapped porous bone scaffold composed of D: ,L: -lactide, epsilon-caprolactone, 1,6-hexanediol and poly(ortho-esters), in which crosslinkage is achieved by photoinitiators, was developed for bone tissue regeneration. Three different polymer mixtures (pure polymer and 30% bioactive glass or alpha-tricalcium phosphate added) were tested in a uni-cortical tibial defect model in eight goats. The polymers were randomly applicated in one of four (6.0 mm diameter) defects leaving a fourth defect unfilled. Biocompatibility and bone healing properties were evaluated by serial radiographies, histology and histomorphometry. The pure polymer clearly showed excellent biocompatibility and moderate osteoconductive properties. The addition of alpha-TCP increased the latter characteristics. This product offers potentials as a carrier for bone healing promoter substances.

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.