The Effects of Negative Pressure Wound Therapy on Vegf and Angiogenesis in Deep Dermal Burn Injury: An Experimental Study.

Burn injuries are the fourth most common type of trauma worldwide, after traffic injuries, falls and interpersonal violence. Vascular endothelial growth factor (VEGF) is one of the most critical proangiogenic factors. Failure in angiogenesis is often associated with chronic, non-healing wounds. This study aimed to compare the effect of sterile gauze with normal saline (NaCl) 0.9%, intermittent negative pressure wound therapy (NPWT), continuous NPWT, and silver sulfadiazine dressing on increasing VEGF and angiogenesis in deep dermal burn injury. This experimental laboratory study involved six Yorkshire pigs. Twenty burns were made on each pig's flank and dorsum areas, which were divided into four treatment groups: sterile gauze with NaCl 0.9%, intermittent NPWT, continuous NPWT, and silver sulfadiazine dressing. Skin biopsies were done on days 1, 3, 7, 14 and 21 to evaluate VEGF histoscore and mean microvascular density (MVD). We used immunohistochemical staining of VEGF-165 as VEGF's protein marker and hematoxylin-eosin (HE) to count the MVD. There was a significant difference in mean VEGF histoscore on evaluation day 14, in which continuous NPWT had the highest score compared to sterile gauze with NaCl 0.9%, intermittent NPWT, and silver sulfadiazine. The elevated VEGF histoscore could significantly increase the MVD.

Les brûlures représentent la 4ème cause mondiale de traumatisme, après les accidents de la voie publique, les chutes et les violences interhumaines. Le facteur vasculaire de croissance endothéliale (FVCE) est un des principaux facteurs de l'angiogénèse qui, lorsqu'elle dysfonctionne, fait passer les plaies à la chronicité. Cette étude compare les effets de pansements au sérum physiologique (NaCl), des thérapies à pression négative (TPN) continue ou intermittente et de la sulfadiazine argentique (SFDA) sur l'augmentation du FVCE et l'angiogénèse dans les brûlures de 2ème degré profond. Cette étude expérimentale a été conduite sur 6 porcs Yorkshire. Vingt brûlures ont été réalisées sur les flancs et régions dorsales de chacun d'eux, réparties en 4 groupes selon leur traitement : NaCl, TPN intermittente, TPN continue et SFDA. Des biopsies cutanées ont été réalisées à J1, 3, 7, 14 et 21 afin d'évaluer histologiquement le score FVCE (par mesure colorimétrique de FVCE-165) et la densité microvasculaire (par coloration hématoxyline- éosine). À j14, la TPN continue permettait d'obtenir le score FVCE le plus élevé, comparativement aux 3 autres pansements et pourrait augmenter la densité microvasculaire.

Magnetic refrigeration material operating at a full temperature range required for hydrogen liquefaction.

Magnetic refrigeration (MR) is a key technique for hydrogen liquefaction. Although the MR has ideally higher performance than the conventional gas compression technique around the hydrogen liquefaction temperature, the lack of MR materials with high magnetic entropy change in a wide temperature range required for the hydrogen liquefaction is a bottle-neck for practical applications of MR cooling systems. Here, we show a series of materials with a giant magnetocaloric effect (MCE) in magnetic entropy change (-∆Sm > 0.2 J cm-3K-1) in the Er(Ho)Co2-based compounds, suitable for operation in the full temperature range required for hydrogen liquefaction (20-77 K). We also demonstrate that the giant MCE becomes reversible, enabling sustainable use of the MR materials, by eliminating the magneto-structural phase transition that leads to deterioration of the MCE. This discovery can lead to the application of Er(Ho)Co2-based alloys for the hydrogen liquefaction using MR cooling technology for the future green fuel society.

Molecular modelling on SARS-CoV-2 papain-like protease: an integrated study with homology modelling, molecular docking, and molecular dynamics simulations.

SARS-CoV-2 PLpro was investigated as a therapeutic target for potent antiviral drugs due to its essential role in not only viral replication but also in regulating the inborn immune response. Several computational approaches, including homology modelling, molecular docking, and molecular dynamics (MD) studies, were employed to search for promising drugs in treating SARS-CoV-2. Eighty-one compounds, sub-structurally similar to the antiviral drug, were used as potential inhibitors of PLpro. From our results, three complexes containing the ligands with Pubchem IDs: 153012995, 12149203, and 123608715 showed lower binding energies than the control (Ritonavir), indicating that they may become promising inhibitors for PLpro. MD was performed in a water solvent to validate the stability of the three complexes. All complexes achieved stable structure during the simulation as no significant fluctuations were observed in the validation parameters. Moreover, the binding energy for each complex was estimated using the MM-GBSA method. Complex 1 was the most stable structure based on the lowest binding energy score and its structure remained in a similar cavity with the docket snapshot. Based on our studies, three ligands were assumed to be potential inhibitors. The ligand of complex 1 may become the most promising antiviral drug against SARS-CoV-2 targeting PLpro.

Implementation of ensemble methods on QSAR Study of NS3 inhibitor activity as anti-dengue agent.

Dengue fever is a disease transmitted by infected mosquitoes. This disease spreads in several countries, especially those with a tropical climate. To date, there is no specific drug that can be used to treat dengue. Use of clinically investigated drugs, such as Balapiravir, is still not effective in inhibiting the activity of virus replication. The design of a drug candidate can be performed by using the non-structural protein 3 (NS3) as target. This study aimed to develop QSAR models to predict the inhibitory activity class of NS3 inhibitors. The classification was performed by using feature importance analysis for selecting the descriptors and three ensemble methods, i.e. random forest (RF), adaptive boosting (AdaBoost), and extremely randomized trees (ERT), for model design and prediction. Hyperparameter tuning was performed to improve the performance of the models. Based on the results, we found that model 9, developed from ERT produced the best performance with values of accuracy and AUC equal to 0.73 and 0.82, respectively. Use of y-scrambling method allowed us to confirm that the model was not related to the chance correlation.

Choosing to make an effort: the role of striatum in signaling physical effort of a chosen action.

The possibility that we will have to invest effort influences our future choice behavior. Indeed deciding whether an action is actually worth taking is a key element in the expression of human apathy or inertia. There is a well developed literature on brain activity related to the anticipation of effort, but how effort affects actual choice is less well understood. Furthermore, prior work is largely restricted to mental as opposed to physical effort or has confounded temporal with effortful costs. Here we investigated choice behavior and brain activity, using functional magnetic resonance imaging, in a study where healthy participants are required to make decisions between effortful gripping, where the factors of force (high and low) and reward (high and low) were varied, and a choice of merely holding a grip device for minimal monetary reward. Behaviorally, we show that force level influences the likelihood of choosing an effortful grip. We observed greater activity in the putamen when participants opt to grip an option with low effort compared with when they opt to grip an option with high effort. The results suggest that, over and above a nonspecific role in movement anticipation and salience, the putamen plays a crucial role in computations for choice that involves effort costs.

Pain relativity in motor control.

Motivational theories of pain highlight its role in people's choices of actions that avoid bodily damage. By contrast, little is known regarding how pain influences action implementation. To explore this less-understood area, we conducted a study in which participants had to rapidly point to a target area to win money while avoiding an overlapping penalty area that would cause pain in their contralateral hand. We found that pain intensity and target-penalty proximity repelled participants' movement away from pain and that motor execution was influenced not by absolute pain magnitudes but by relative pain differences. Our results indicate that the magnitude and probability of pain have a precise role in guiding motor control and that representations of pain that guide action are, at least in part, relative rather than absolute. Additionally, our study shows that the implicit monetary valuation of pain, like many explicit valuations (e.g., patients' use of rating scales in medical contexts), is unstable, a finding that has implications for pain treatment in clinical contexts.