The Novel Chiral 2(5H)-Furanone Sulfones Possessing Terpene Moiety: Synthesis and Biological Activity.

Over the past decades, 2(5H)-furanone derivatives have been extensively studied because of their promising ability to prevent the biofilm formation by various pathogenic bacteria. Here, we report the synthesis of a series of optically active sulfur-containing 2(5H)-furanone derivatives and characterize their biological activity. Novel thioethers were obtained by an interaction of stereochemically pure 5-(l)-menthyloxy- or 5-(l)-bornyloxy-2(5H)-furanones with aromatic thiols under basic conditions. Subsequent thioethers oxidation by an excess of hydrogen peroxide in acetic acid resulted in the formation of the corresponding chiral 2(5H)-furanone sulfones. The structure of synthesized compounds was confirmed by IR and NMR spectroscopy, HRMS, and single crystal X-ray diffraction. The leading compound, 26, possessing the sulfonyl group and l-borneol moiety, exhibited the prominent activity against Staphylococcus aureus and Bacillus subtilis with MICs of 8 µg/mL. Furthermore, at concentrations of 0.4-0.5 µg/mL, the sulfone 26 increased two-fold the efficacy of aminoglycosides gentamicin and amikacin against S. aureus. The treatment of the model-infected skin wound in the rat with a combination of gentamicin and sulfone 26 speeded up the bacterial decontamination and improved the healing of the wound. The presented results provide valuable new insights into the chemistry of 2(5H)-furanone derivatives and associated biological activities.

The Automatization of the Gait Analysis by the Vicon Video System: A Pilot Study.

The quality of modern measuring instruments has a strong influence on the speed of diagnosing diseases of the human musculoskeletal system. The research is focused on automatization of the method of gait analysis. The study involved six healthy subjects. The subjects walk straight. Each subject made several gait types: casual walking and imitation of a non-standard gait, including shuffling, lameness, clubfoot, walking from the heel, rolling from heel to toe, walking with hands in pockets, and catwalk. Each type of gait was recorded three times. For video fixation, the Vicon Nexus system was used. A total of 27 reflective markers were placed on the special anatomical regions. The goniometry methods were used. The walk data were divided by steps and by step phases. Kinematic parameters for estimation were formulated and calculated. An approach for data clusterization is presented. For this purpose, angle data were interpolated and the interpolation coefficients were used for clustering the data. The data were processed and four cluster groups were found. Typical angulograms for cluster groups were presented. For each group, average angles were calculated. A statistically significant difference was found between received cluster groups.

Extension of the Voronoi Diagram Algorithm to Orthotropic Space for Material Structural Design.

Nowadays, the interaction of additive technologies and methods for designing or optimizing porous structures has yielded good results. Construction with complex microarchitectures can be created using this approach. Varying the microarchitecture leads to changes in weight and mechanical properties. However, there are problems with geometry reconstruction when dealing with complex microarchitecture. One approach is to use Voronoi cells for geometry reconstruction. In this article, an extension of the Voronoi diagram algorithm to orthotropic space for material structural design is presented. The inputs for the method include porosity, ellipticity, and ellipticity direction fields. As an example, a beam with fixed end faces and center kinematic loading was used. To estimate robust results for different numbers of clusters, 50, 75, and 100 clusters are presented. The porosity for smoothed structures ranged from 21.5% up to 22.8%. The stress-strain state was determined for the resulting structures. The stiffness for the initial and smoothed structures was the same. However, in the case of 75 and 100 clusters, local stress factors appeared in the smoothed structure. The maximum von Mises stress decreased by 20% for all smoothed structures in the area of kinematic loading and increased by 20% for all smoothed structures in the area of end faces.

Consecutive Transcutaneous and Epidural Spinal Cord Neuromodulation to Modify Clinical Complete Paralysis-the Proof of Concept.

Objective: To evaluate the effect of transcutaneous (tSCS) and epidural electrical spinal cord stimulation (EES) in facilitating volitional movements, balance, and nonmotor functions, in this observational study, tSCS and EES were consecutively tested in 2 participants with motor complete spinal cord injury (SCI). Participants and Methods: Two participants (a 48-year-old woman and a 28-year-old man), both classified as motor complete spinal injury, were enrolled in the study. Both participants went through a unified protocol, such as an initial electrophysiological assessment of neural connectivity, consecutive tSCS and EES combined with 8 wks of motor training with electromyography (EMG) and kinematic evaluation. The study was conducted from May 1, 2019, to December 31, 2021. Results: In both participants, tSCS reported a minimal improvement in voluntary movements still essential to start tSCS-enabled rehabilitation. Compared with tSCS, following EES showed immediate improvement in voluntary movements, whereas tSCS was more effective in improving balance and posture. Continuous improvement in nonmotor functions was found during tSCS-enabled and then during EES-enabled motor training. Conclusion: Results report a significant difference in the effect of tSCS and EES on the recovery of neurologic functions and support consecutive tSCS and EES applications as a potential therapy for SCI. The proposed approach may help in selecting patients with SCI responsive to neuromodulation. It would also help initiate neuromodulation and rehabilitation therapy early, particularly for motor complete SCI with minimal effect from conventional rehabilitation.

Functional State of the Motor Centers of the Lumbar Spine after Contusion (Th8-Th9) with Application of Methylprednisolone-Copolymer at the Site of Injury.

Spinal cord injuries must be treated as soon as possible. Studies of NASCIS protocols have questioned the use of methylprednisolone therapy. This study aimed to evaluate the effect of local delivery of methylprednisolone succinate in combination with a tri-block copolymer in rats with spinal cord injury. The experiments were conducted in accordance with the bioethical guidelines. We evaluated the state of the motor centers below the level of injury by assessing the amplitude of evoked motor responses in the hind limb muscles of rats during epidural stimulation. Kinematic analysis was performed to examine the stepping cycle in each rat. Trajectories of foot movements were plotted to determine the range of limb motion, maximum foot lift height, and lateral deviation of the foot in rats on the 21st day after spinal cord injury. We have shown that the local application of methylprednisolone succinate in combination with block copolymer leads to recovery of center excitability by 21 days after injury. In rats, they recovered weight-supported locomotion, directional control of walking, and balance. The proposed assessment method provides valuable information on gait disturbances following injury and can be utilized to evaluate the quality of therapeutic interventions.

The Effect of Surface Processing on the Shear Strength of Cobalt-Chromium Dental Alloy and Ceramics.

Porcelain fused to metal is widespread dental prosthetic restoration. The survival rate of metal-ceramic restorations depends not only on the qualifications of dentists, dental technicians but also on the adhesive strength of ceramics to a metal frame. The goal of the research is to determine the optimal parameters of the surface machining of the metal frame to increase the adhesion of metal to ceramics. Adhesion of cobalt-chromium alloy and ceramics was investigated. A profilometer and a scanning electron microscope were used to analyze the morphology. To estimate the adhesion the shear strength was measured by the method based on ASTM D1002-10. A method of surface microrelief formation of metal samples by plasma-electrolyte treatment has been developed. Regimes for plasma-electrolyte surface treatment were investigated according to current-voltage characteristics and a surface roughness parameter. The samples were subjected to different surface machining techniques such as polishing, milling, sandblasting (so-called traditional methods), and plasma-electrolyte processing. Morphology of the surface for all samples was studied and the difference in microrelief was shown. The roughness and adhesive strength were measured for samples either. As a result, the mode for plasma- electrolytic surface treatment under which the adhesive strength was increased up to 183% (compared with the traditional methods) was found.

Structural Design Method for Constructions: Simulation, Manufacturing and Experiment.

The development of additive manufacturing technology leads to new concepts for design implants and prostheses. The necessity of such approaches is fueled by patient-oriented medicine. Such a concept involves a new way of understanding material and includes complex structural geometry, lattice constructions, and metamaterials. This leads to new design concepts. In the article, the structural design method is presented. The general approach is based on the separation of the micro- and macro-mechanical parameters. For this purpose, the investigated region as a complex of the basic cells was considered. Each basic cell can be described by a parameters vector. An initializing vector was introduced to control the changes in the parameters vector. Changing the parameters vector according to the stress-strain state and the initializing vector leads to changes in the basic cells and consequently to changes in the microarchitecture. A medium with a spheroidal pore was considered as a basic cell. Porosity and ellipticity were used for the parameters vector. The initializing vector was initialized and depended on maximum von Mises stress. A sample was designed according to the proposed method. Then, solid and structurally designed samples were produced by additive manufacturing technology. The samples were scanned by computer tomography and then tested by structural loads. The results and analyses were presented.

Design and Optimization Lattice Endoprosthesis for Long Bones: Manufacturing and Clinical Experiment.

The article is devoted to the construction of lattice endoprosthesis for a long bone. Clinically, the main idea is to design a construction with the ability to improve bone growth. The article presents the algorithm for such a design. The construction should be produced by additive manufacturing. Such an approach allows using not only metallic materials but also ceramics and polymers. The algorithm is based on the influence function as a method to describe the elementary cell geometry. The elementary cell can be described by a number of parameters. The influence function maps the parameters to local stress in construction. Changing the parameters influences the stress distribution in the endoprosthesis. In the paper, a bipyramid was used as an elementary cell. Numerical studies were performed using the finite element method. As a result, manufacturing construction is described. Some problems for different orientations of growth are given. The clinical test was done and histological results were presented.

Anti-biofilm and wound-healing activity of chitosan-immobilized Ficin.

Biofouling is among the key factors slowing down healing of acute and chronic wounds. Here we report both anti-biofilm and wound-healing properties of the chitosan-immobilized Ficin. The proposed chitosan-adsorption approach allowed preserving ~90% of the initial total activity of the enzyme (when using azocasein as a substrate) with stabilization factor of 4.9, and ~70% of its specific enzymatic activity. In vitro, the chitosan-immobilized Ficin degraded staphylococcal biofilms, this way increasing the efficacy of antimicrobials against biofilm-embedded bacteria. In vivo, in the presence of Ficin (either soluble or immobilized), the S.aureus-infected skin wound areas in rats reduced twofold after 4 instead of 6 days treatment. Moreover, topical application of the immobilized enzyme resulted in a 3-log reduction of S. aureus cell count on the wound surfaces in 6 days, compared to more than 10 days required to achieve the same effect in control. Additional advantages include smoother reepithelisation, and new tissue formation exhibiting collagen structure characteristics closely reminiscent of those observed in the native tissue. Taken together, our data suggest that both soluble and immobilized Ficin appear beneficial for the treatment of biofilm-associated infections, as well as speeding up wound healing and microbial decontamination.