Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a ...single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset.
We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0–1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0–1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993.
Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89–89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio OR 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI –1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044).
Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary.
The Russian Academy of Sciences.
Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space ...travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.
An international group of spaceflight researchers detail how spaceflight affects human biology from the molecular to physiological level and identify key challenges for making space exploration compatible with human health.
Future multi-year crewed planetary missions will motivate advances in aerospace nutrition and telehealth. On Earth, the Human Cell Atlas project aims to spatially map all cell types in the human ...body. Here, we propose that a parallel Human Cell Space Atlas could serve as an openly available, global resource for space life science research. As humanity becomes increasingly spacefaring, high-resolution omics on orbit could permit an advent of precision spaceflight healthcare. Alongside the scientific potential, we consider the complex ethical, cultural, and legal challenges intrinsic to the human space omics discipline, and how philosophical frameworks may benefit from international perspectives.High-resolution omics data have facilitated the ongoing Human Cell Atlas project. In this Perspective, Rutter and colleagues propose that a parallel Human Cell Space Atlas initiative would provide a platform for spaceflight-associated research and healthcare.
Link for citation: Azin A.V., Bogdanov E.P., Vasilyev A.V., Ponomarev S.A., Ponomarev S.V., Rikkonen S.V. Configurations of ultrasonic emitter resonance modes for unilateral access to an object. ...Bulletin of the Tomsk Polytechnic University. Geo Аssets Engineering, 2023, vol. 334, no. 10, рр. 199-209. In Rus.
Relevance. To prepare high-viscosity oil for transport, a number of methods are used in practice: thermal, chemical and the method of physical influences. Ultrasonic exposure of hydrocarbon raw materials is one of the physical methods. It is necessary to develop an effective method for tuning an ultrasonic emitter for maximum energy transfer into a multilayer technological medium. Aim: to study resonant operating modes of an ultrasonic emitter in a multilayer system with unilateral access to the object with simplified design of a resonance type ultrasonic emitter. Objects: oscillating system of an ultrasonic resonant type emitter, multilayer system, physical model of a system «ultrasonic emitter – multilayer system». Methods: mathematical modeling of linear oscillating system to determine the properties of oscillating system influence and technological factors on the form of vibration oscillations and on the amplitude-frequency characteristics of the system; experimental research on the basis of the physical model «ultrasonic emitter – multilayer system». Results. The authors have revealed a physical feature of the oscillatory system operation, which consists in the fact that at resonance the form of oscillations of the force signals of a multilayer piezoactor and vibration acceleration signals are purely harmonic in nature. This effect extends to operation of a resonant-type ultrasonic emitter in a short-circuit mode on a multilayer system. It was found that force and vibration acceleration amplitude-frequency characteristics of a multilayer piezoactor are similar to each other. Based on the analysis of theoretical and experimental data, the authors developed the method for adjusting the resonant operating modes of an ultrasonic emitter with unilateral access to an object. This allows simplification and reduction in the emitter design cost. The method for setting up oscillatory systems is applicable for laboratory and industrial installations. Conclusion. The research results show that in practice, harmonic shape of acceleration and force signals, as well as force amplitude of a multilayer piezoactor can be used as criteria for determining and adjusting the resonance of an oscillatory system. The oscillatory system of a resonant-type ultrasonic emitter can be tuned to resonance according to the shape and amplitude of the signal from the force sensor of the multilayer piezoactor. The force sensor is located in series with the multilayer piezoactor and does not require additional structural elements for its fastening. The ultrasonic emitter design is greatly simplified due to the absence of a vibration acceleration sensor. The method of adjusting the resonance of an oscillatory system using only a force sensor is also applied when operating a resonant-type ultrasonic emitter to a multilayer mechanical system. The developed design and technique for tuning the oscillatory system of a resonant-type ultrasonic emitter can be conveniently used when influencing process fluids through the walls of tanks and storage tanks.
The Bransfield Strait is a relatively deep and narrow channel between the South Shetland Islands and the Antarctic Peninsula contributing to the water transport between the Pacific and Atlantic ...sectors of the Southern Ocean. The strait can be divided into three deep separate basins, namely, the western, central, and eastern basins. The sources of deep waters in the three basins are different, leading to differences in thermohaline properties and water density between the basins. The difference in water density should in turn cause intense deep currents from one basin to another through narrow passages over the sills separating the basins. However, there are still no works dedicated to such possible overflows in the Bransfield Strait. In this study, we report our new CTD and LADCP measurements performed in 2022 over the watersheds between the basins. Quasisimultaneous observations of the main circulation patterns carried out at several sections allowed us to analyze the evolution of thermohaline and kinematic structures along the Bransfield Strait. Volume transports of waters in the strait were estimated on the basis of direct velocity observations. These new data also indicate the existence of intense and variable deep current between the central and eastern basins of the strait. The analysis of historical data shows that the mean flow is directed from the central to the eastern basin. In addition, LADCP data suggest the intensification of the flow in the narrow part of the sill between the basins, and the possible mixing of deep waters at this location.
The development of flexible and low-cost methods of surface functionalization to fight infection at the early stage is an urgent scientific task. Herein, polymerization in low-pressure plasma rich in ...COOH species and carbodiimide chemistry methods were utilized to immobilize four different therapeutic agents (antibiotic (gentamicin), antimicrobial peptide (indolicidin), anti-adhesive molecules (heparin) and nitroxide radicals (2,2,5,5-tetramethyl-3-carboxyl-pyrrolidine-1-oxyl)) on the surface of nanostructured biocompatible TiCaPCON films to impart antibacterial characteristics. The polymers deposited from COOH-rich plasma showed decent stability in phosphate-buffered saline solution and were successfully used for the immobilization of different therapeutic agents via ionic or covalent bond. The bactericide attachment was proved by FTIR spectroscopy and XPS analysis. All samples with grafted therapeutic agents were hydrophilic with water contact angle values in the range of 26–56°. Bactericide release tests indicated the maximum concentration of therapeutic agents in the case of ionic immobilization. In case of covalent immobilization, fast initial release observed over 24 h was followed by slower leaching in the next 24 h (indolicidin), 48 h (heparin), and 96 h (gentamicin). The pH-sensitive COOH plasma polymer degradation and gentamicin release were demonstrated. The bactericide-linked films showed noticeable reduction of the antibiotic-sensitive E. coli U20 strain and, except indolicidin-immobilized samples, effectively inhibited growth of the antibiotic-resistant E. coli K261 strain at their initial concentration of 104 CFU/mL. The films with nitroxide radicals not only exhibited the highest antibacterial activity against E. coli K261 cells (100% after 8 h), but also prevented the biofilm formation.
Display omitted
•Low pressure plasma polymerization of nanostructured TiCaPCON films•Covalently and electrostatically attached nitroxide radicals, gentamicin, heparin, and indolicidin•All surface-bonded bactericidal agents were effective against antibiotic-sensitive E. coli strain.•Gentamicin, heparin, and NO radicals inhibited the growth of antibiotic-resistant E. coli strain.•Ionically bound nitroxide radicals showed the highest antibacterial activity and best reproducibility.
This study aimed to reveal electrophysiological markers of communicative and cognitive dysfunctions of different severity in children with autism spectrum disorder (ASD). Eyes-opened ...electroencephalograms (EEGs) of 42 children with ASD, divided into two groups according to the severity of their communicative and cognitive dysfunctions (24 with severe and 18 children with less severe ASD), and 70 age-matched controls aged 4–9 years were examined by means of spectral and group independent component (gIC) analyses. A predominance of theta and beta EEG activity in both groups of children with ASD compared to the activity in the control group was found in the global gIC together with a predominance of beta EEG activity in the right occipital region. The quantity of local gICs with enhanced slow and high-frequency EEG activity (within the frontal, temporal, and parietal cortex areas) in children 4–9 years of age might be considered a marker of cognitive and communicative dysfunction severity.
•EEG markers of cognitive and communicative dysfunctions were pronounced in the theta, beta bands and characterized by global and local gICs.•The spectral power of gICs in ASD group with severe dysfunctions was higher than in Controls in more regions than in ASD with mild dysfunctions.•Attention in ASD group was inversely correlated with theta spectral power, theta/alpha, theta/beta power ratios in the parietal cortex.
The relevance of this study is caused by the fact that in order to increase the efficiency (productivity) of the ultrasound method for preparing high-viscosity oil for transport it is necessary to ...take into account all the construction features of the ultrasound emitter in order to fully complete energy matching of the oscillatory system «emitter–load». The aim of the research is to develop a mathematical model of an ultrasound resonant emitter accounting for the effect of deformation of the emitter body and oscillations of a multilayer piezo actuator on its amplitude-frequency characteristics in order to obtain the total energy characteristics of the system. Objects: the design of the ultrasound resonant emitter, amplitude-frequency characteristics. Methods: mathematical modeling of an ultrasound resonant emitter, taking into account the oscillating processes of the movable parts inertia of the structure, the mobility of a emitter body part and the oscillating processes of a multilayer piezo actuator. Results. The mathematical model makes it possible to calculate the amplitude-frequency characteristics of the oscillatory system accounting for deformations of the ultrasound emitter body and oscillations of a multilayer piezo actuator; to determine the resonant frequencies of the system; to choose the construction of the emitter body and piezo package. Results of the theoretical calculations show very good agreement with experimental data with the deviation of no more than 15 %. Conclusions. The results of the study showed that in order to obtain reliable information on operation of ultrasound resonance emitter, the influence of the rigidity of the body and internal oscillations of the multilayer piezoactuator must be taken into account in the analytical calculations. The deformation of a part of the ultrasound emitter body by the use of inspection windows increases the acceleration of the working pusher as compared to the operation of the radiator ultrasound emitter with a completely rigid body, thereby increasing the coefficient of electrical energy into mechanical one. The mathematical model of the ultrasound resonant emitter makes it possible to determine the oscillation system frequencies at which the maximum energy conversion coefficient is observed and to estimate the necessary accuracy of the energy source frequency setting.
We discuss experimental and theoretical studies of the generation of the third terahertz (THz) frequency harmonic in thin films of Bi2Se3 and Bi2-xSbxTe3-ySey (BSTS) topological insulators (TIs) and ...the generation of THz radiation in photoconductive antennas based on the TI films. The experimental results, supported by the developed kinetic theory of third harmonic generation, show that the frequency conversion in TIs is highly efficient because of the linear energy spectrum of the surface carriers and fast energy dissipation. In particular, the dependence of the third harmonic field on the pump field remains cubic up to the pump fields of 100 kV/cm. The generation of THz radiation in TI-based antennas is obtained and described for the pump, with the energy of photons corresponding to the electron transitions to higher conduction bands. Our findings open up possibilities for advancing TI-based films into THz photonics as efficient THz wave generators and frequency converters.
PDF
