Numerical Simulation of the Bearing Capacity of Variotropic Short Concrete Beams Reinforced with Polymer Composite Reinforcing Bars.

One of the disadvantages of reinforced concrete is the large weight of structures due to the steel reinforcement. A way to overcome this issue and develop new types of reinforcing elements is by using polymer composite reinforcement, which can successfully compensate for the shortcomings of steel reinforcement. Additionally, a promising direction is the creation of variotropic (transversely isotropic) building elements. The purpose of this work was to numerically analyze improved short bending concrete elements with a variotropic structure reinforced with polymer composite rods and to determine the prospects for the further extension of the results obtained for long-span structures. Numerical models of beams of a transversally isotropic structure with various types of reinforcement have been developed in a spatially and physically nonlinear formulation in ANSYS software considering cracking and crashing. It is shown that, in combination with a stronger layer of the compressed zone of the beam, carbon composite reinforcement has advantages and provides a greater bearing capacity than glass or basalt composite. It has been proven that the use of the integral characteristics of concrete and the deflections of the elements are greater than those when using the differential characteristics of concrete along the height of the section (up to 5%). The zones of the initiation and propagation of cracks for different polymer composite reinforcements are determined. An assessment of the bearing capacity of the beam is given. A significant (up to 146%) increase in the forces in the reinforcing bars and a decrease in tensile stresses (up to 210-230%) were established during the physically non-linear operation of the concrete material. The effect of a clear redistribution of stresses is in favor of elements with a variotropic cross section in height.

Strength of Compressed Reinforced Concrete Elements Reinforced with CFRP at Different Load Application Eccentricity.

Currently, many studies are devoted to the use of polymer composite materials to increase the strength and stability of concrete elements. In compressed reinforced concrete elements, the bearing capacity depends on the eccentricity of the external application of the external force and the corresponding stress-strain state, as well as the location and number of composite materials glued to the surface of the structure. The choice of a scheme for placing composite materials depending on the stress state of the structure is an urgent scientific problem. At the same time, the issue of central compression and the compression of columns with large eccentricities has been well studied. However, studies conducted in the range of average eccentricities often have conflicting results, which is the problem area of this study. The primary aim of this study was to increase the strength and stiffness of compressed reinforced concrete elements reinforced with composite materials, as well as a comparative analysis of the bearing capacity of ten different combinations of external longitudinal, transverse, and combined reinforcement. The results of testing 16 compressed columns under the action of various eccentricities of external load application (e0/h = 0; 0.16; 0.32) are presented. It is shown that the use of composite materials in strengthening structures increases the bearing capacity up to 41%, and the stiffness of the sections increases up to 30%. Based on the results of the study, recommendations are proposed for improving the calculation method for inflexible columns reinforced in the transverse direction, which take the work of concrete under the conditions of a three-dimensional stress state into consideration.

Aortography Keypoint Tracking for Transcatheter Aortic Valve Implantation Based on Multi-Task Learning.

Currently, transcatheter aortic valve implantation (TAVI) represents the most efficient treatment option for patients with aortic stenosis, yet its clinical outcomes largely depend on the accuracy of valve positioning that is frequently complicated when routine imaging modalities are applied. Therefore, existing limitations of perioperative imaging underscore the need for the development of novel visual assistance systems enabling accurate procedures. In this paper, we propose an original multi-task learning-based algorithm for tracking the location of anatomical landmarks and labeling critical keypoints on both aortic valve and delivery system during TAVI. In order to optimize the speed and precision of labeling, we designed nine neural networks and then tested them to predict 11 keypoints of interest. These models were based on a variety of neural network architectures, namely MobileNet V2, ResNet V2, Inception V3, Inception ResNet V2 and EfficientNet B5. During training and validation, ResNet V2 and MobileNet V2 architectures showed the best prediction accuracy/time ratio, predicting keypoint labels and coordinates with 97/96% accuracy and 4.7/5.6% mean absolute error, respectively. Our study provides evidence that neural networks with these architectures are capable to perform real-time predictions of aortic valve and delivery system location, thereby contributing to the proper valve positioning during TAVI.

Randomized Clinical Trial of Surgical vs. Percutaneous vs. Hybrid Revascularization in Multivessel Coronary Artery Disease: Residual Myocardial Ischemia and Clinical Outcomes at One Year-Hybrid coronary REvascularization Versus Stenting or Surgery (HREVS).

AIM: Optimal revascularization strategy in multivessel (MV) coronary artery disease (CAD) eligible for percutaneous management (PCI) and surgery remains unresolved. We evaluated, in a randomized clinical trial, residual myocardial ischemia (RI) and clinical outcomes of MV-CAD revascularization using coronary artery bypass grafting (CABG), hybrid coronary revascularization (HCR), or MV-PCI. METHODS: Consecutive MV-CAD patients (n = 155) were randomized (1 : 1 : 1) to conventional CABG (LIMA-LAD plus venous grafts) or HCR (MIDCAB LIMA-LAD followed by PCI for remaining vessels) or MV-PCI (everolimus-eluting CoCr stents) under Heart Team agreement on equal technical and clinical feasibility of each strategy. SPECT at 12 months (primary endpoint of RI that the trial was powered for; a measure of revascularization midterm efficacy and an independent predictor of long-term prognosis) preceded routine angiographic control. RESULTS: Data are given, respectively, for the CABG, HCR, and MV-PCI arms. Incomplete revascularization rate was 8.0% vs. 7.7% vs. 5.7% (p=0.71). Hospital stay was 13.8 vs. 13.5 vs. 4.5 days (p < 0.001), and sick-leave duration was 23 vs. 16 vs. 8 weeks (p < 0.001). At 12 months, RI was 5 (2, 9)% vs. 5 (3, 7)% vs. 6 (3, 10)% (median; Q1, Q3) with noninferiority p values of 0.0006 (HCR vs. CABG) and 0.016 (MV-PCI vs. CABG). Rates of angiographic graft stenosis/occlusion or in-segment restenosis were 20.4% vs. 8.2% vs. 5.9% (p=0.05). Clinical target vessel/graft failure occurred in 12.0% vs. 11.5% vs. 11.3% (p=0.62). Major adverse cardiac and cerebral event (MACCE) rate was similar (12% vs. 13.4% vs. 13.2%; p=0.83). CONCLUSION: In this first randomized controlled study comparing CABG, HCR, and MV-PCI, residual myocardial ischemia and MACCE were similar at 12 months. There was no midterm indication of any added value of HCR. Hospital stay and sick-leave duration were shortest with MV-PCI. While longer-term follow-up is warranted, these findings may impact patient and physician choices and healthcare resources utilization. This trial is registered with NCT01699048.

Biological markers and cardiac remodelling following the myocardial infarction.

AIM: To assess growth stimulating factor ST2 and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels in the sera of myocardial infraction (MI) patients, and their correlation with the adaptive and maladaptive variants of cardiac remodelling. METHODS: 87 patients (65 male, 22 females; 67±8.36 years) with ST-elevated MI were included in this study, and 67 patients had an adaptive, physiological, while 20 patients had a maladaptive, pathological variant of myocardium remodelling. RESULTS: On day 1, ST2 and NT-proBNP levels were shown to increase 2.4 and 4.5 folds, respectively, compared with those in the control. ST2 levels in patients with maladaptive remodelling were 1.5-fold higher than those in the adaptive remodelling group. On day 12, a decrease in ST2 levels was observed in both groups. NT-proBNP levels increased 1.8 folds in both groups on day 1, compared with those in the controls. Increased ST2 levels on day 1 after MI were shown to increase the risk of maladaptive remodelling 4.5 folds, while high NT-proBNP levels increased this risk 2.3 times. CONCLUSIONS: ST2 level determination allows us to predict the risk of maladaptive remodelling with a higher sensitivity and specificity than using NT-proBNP levels.

Pleiotropic effects of hemagglutinin amino acid substitutions of influenza A(H1N1)pdm09 virus escape mutants.

In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We investigated pH optimum of fusion, temperatures of HA heat inactivation, in vivo and in vitro replication kinetics, and connectivity with panel of sera of survivors patients in different epidemic seasons of the previously obtained influenza H1 escape mutants. Our results showed that N133D (H3 numbering) mutation significantly lowered the pH of fusion optimum. Several amino acid substitutions, including K163 N, Q192 L, D190E, G228E, and K285 M, reduced the stability of HA as determined by heat inactivation, whereas A198E substitution is associated with significant increase in HA thermostability compared to the wild-type virus. We found that amino acid change D190 N was associated with a significant decrease in viral growth in eggs and mice. Our potential antigenic variants, except readapted variant, which contained A198E mutation, did not reach fixation in infected people. Overall, a co-variation between antigenic specificity and different HA phenotypic properties was demonstrated.

Effect of different doses of statins on the development of type 2 diabetes mellitus in patients with myocardial infarction.

BACKGROUND: Cardiovascular diseases and type 2 diabetes mellitus (T2DM) may have common developmental mechanisms associated with lipid metabolism disorders. Dyslipidemia and progression of atherosclerosis in people with T2DM are accompanied by an increase in cardiovascular mortality. This study examined the dose-dependent action of atorvastatin on carbohydrate metabolism and adipokine status in patients within 12 months after myocardial infarction (MI). METHODS: A total of 156 male MI patients who had received atorvastatin 20 mg/day (78 patients) or 40 mg/day (78 patients) starting from day 1 of onset were enrolled. Glucose, insulin, C-peptide, resistin, adiponectin, and ghrelin levels were measured at baseline, day 12, and months 3 and 12. Patients were monitored for new incidences of T2DM for 12 months after MI. RESULTS: For acute phase MI, patients had moderate insulin resistance, hyperglycemia, and hyper-insulinemia, high leptin and resistin levels, and low ghrelin and adiponectin levels. Atorvastatin 20 mg/day was more effective at correcting the imbalances. Patients taking atorvastatin 40 mg/day (group 2) following MI showed increases in levels of glucose, insulin, and C-peptide and insulin resistance progression after 12 months of therapy, as evidenced by increased quantitative insulin sensitivity check index scores and detection of new T2DM cases. CONCLUSION: Atorvastatin improved adipokine profiles and ghrelin levels, with low doses showing more significant effects. Atorvastatin dose prescribed for MI patients should take into account the degree of insulin resistance and adipokine status.

Effects of hemagglutinin amino acid substitutions in H9 influenza A virus escape mutants.

We assessed the pH optimum of fusion, HA thermostability, and in vitro replication kinetics of previously obtained influenza H9 escape mutants. The N198S mutation significantly increased the optimum pH of fusion. Four HA changes, S133N, T189A, N198D, and L226Q, were associated with a significant increase in HA thermostability compared to the wild-type virus. HA amino acid changes at positions 116, 133, 135, 157, 162, and 193 significantly decreased the replicative ability of H9 escape mutants in vitro. Monitoring of pleiotropic effects of the HA mutations found in H9 escape mutants is essential for accurate prediction of all possible outcomes of immune selection of H9 influenza A viruses.

Prognostic Value of Soluble ST2 During Hospitalization for ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Studying the role of soluble ST2 (sST2) during hospitalization for myocardial infarction (MI) can be helpful for predicting the course of the hospitalization and development of complications. METHODS: We included 88 patients with MI (median age, 58 yr). Depending on the course of the hospitalization, the patients were divided into two groups: the favorable (n=58) and unfavorable (n=30) outcome groups. On days 1 and 12 after MI, serum sST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured by ELISA. RESULTS: On day 1, the concentrations of sST2 and NT-proBNP increased 2.4- and 4.5-fold, compared with the controls. Measurements on day 12 showed a significant decrease in the sST2 level (P=0.001), whereas the NT-proBNP level did not change. On day 1, the sST2 level in the unfavorable outcome group was 2-fold higher than that in the favorable outcome group and 3.7-fold higher than in the controls. On day 12, the marker level decreased in both groups. On day 1, the NT-proBNP level in the unfavorable outcome group was 6.8-fold higher than in the controls and 1.8-fold higher than in the favorable outcome group. On day 12, the level of NT-proBNP remained elevated in both groups. Determining the levels of both sST2 and NT-proBNP increases their diagnostic significance (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.7-3.2; areas under curve [AUC] 0.89; P=0.004). CONCLUSIONS: The level of sST2 is a more sensitive indicator during MI hospitalization than NT-proBNP.

Pleiotropic effects of amino acid substitutions in H5 hemagglutinin of influenza A escape mutants.

We believe that the monitoring of pleiotropic effects of the hemagglutinin (HA) mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. In the present study, we assessed multiple characteristics of antibody-selected HA mutations. We examined the pH optimum of fusion, HA heat inactivation, affinity to sialyl receptors, and in vitro and in vivo replication kinetics of various influenza H5 escape mutants. Several amino acid substitutions, including T108I, K152E, R162G, and K218N, reduced the stability of HA as determined by heat inactivation, whereas S128L and T215A substitutions were associated with significant increases in HA thermostability compared to the respective wild-type viruses. HA mutations at positions 108, 113, 115, 121, 123, 128, 162, and 190 and substitutions at positions 123, 199, and 215 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. The T108I substitution lowered the pH optimum of fusion and HA temperature stability while increasing viral replicative ability. Taken together, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated.

Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants.

In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential.

Escape mutants of pandemic influenza A/H1N1 2009 virus: variations in antigenic specificity and receptor affinity of the hemagglutinin.

A panel of 6 neutralizing monoclonal antibodies (MAbs) raised against A/Moscow/IIV01/2009 (H1N1) virus isolated during the 2009 pandemic was used for the selection of 26 escape mutants. The mutants were characterized in immune cross-reactions with the panel of MAbs. The sequencing of the mutant HA genes revealed 5 amino acid positions recognized by monoclonal antibodies: 129, 156, 158, 159, and 190 (H3 numbering). The amino acid positions were distributed in two epitopes belonging to antigenic sites Sa and Sb. The mutant HAs exhibited variations in the affinity to synthetic high molecular mass sialic acid-containing receptor analogues. Results are discussed in connection with the antigenic drift potential of the "swine-like" pandemic 2009 influenza virus.

Antigenic epitopes in the hemagglutinin of Qinghai-type influenza H5N1 virus.

The highly pathogenic avian influenza H5N1 viruses have become widespread and evolved into several clades. In our previous studies, the antigenic sites of the H5 hemagglutinin (HA) were characterized by selection and sequencing of escape mutants. In the present studies we analyzed the antigenic epitopes recognized by monoclonal antibodies against avian influenza A/Duck/Novosibirsk/56/05 (H5N1) virus isolated in western Siberia and belonging to subclade 2.2 of the H5N1 viruses. The analysis revealed several antigenically relevant positions of amino acid residues in the globular head of the HA not encountered earlier in the escape mutants of the H5 subtype. The newly recognized positions (113, 117, 118, 120, and 123, mature H5 numbering) are concentrated in an area adjacent to the region described in earlier studies as corresponding to site B in H3 HA, but extending far beyond this area. The amino acid positions recognized by the monoclonal antibodies against A/Duck/Novosibirsk/56/05 (H5N1) virus differ from the positions recognized by the monoclonal antibodies against H5N2 influenza viruses. The data suggest that the evolution of the HA of H5 avian influenza viruses is associated not only with the changes of antigenic epitopes recognized by antibodies, but also with a change in the dominance of the immunogenicity of different sites in the HA.

Adjustment of receptor-binding and neuraminidase substrate specificities in avian-human reassortant influenza viruses.

Balanced action of hemagglutinin (HA) and neuraminidase (NA) is an important condition of influenza virus efficient replication, but a role of HA and NA specificities at oligosaccharide level in maintaining such a balance remains poorly studied. Avian virus HA binds exclusively and NA digests efficiently alpha2-3-sialylated carbohydrate chains, while human virus HA interacts with alpha2-6 chains and low-active NA cleaves both alpha2-3- and alpha2-6-sialosides. Reassortment between viruses leading to appearance of avian virus HA and human virus NA on the virion surface often resulted in decreasing the replicative potential of the formed variants because of disturbance of a functional balance between "alien" HA and NA. A restoration of the reassortant productivity happened due to the appearance of amino acid substitutions in HA and, sometimes, NA. Here, a role of NA and HA oligosaccharide specificities in a restoration of HA-NA functional balance in high-yield passage variants was studied. Postreassortment changes in HA receptor-binding and NA substrate specificities for three reassortant/passage variant virus pairs towards 3'SiaLac, 3'SiaLacNAc, SiaLe(c), SiaLe(a), SiaLe(x), 6'SiaLac, and 6'SiaLacNAc were determined. Selection of the high-yield variants of the human-avian reassortants led either to twofold decrease in the affinity of HA for most alpha2-3-sialosides and the appearance of affinity for alpha2-6-sialosides (H3N2 reassortant), or to decreasing the HA affinity for SiaLe(c) and SiaLe(a) (H3N1 reassortant), or to enhancing the ability of NA to discriminate between alpha2-3/2-6 substrates (H4N1 reassortant). Thus, all postreassortment changes in oligosaccharide specificities of "alien" HA and NA were directed towards their adjustment to each other, but by different manner.

Epitope mapping of the hemagglutinin molecule of a highly pathogenic H5N1 influenza virus by using monoclonal antibodies.

We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus containing A/Vietnam/1203/04 (H5N1) deltaHA and neuraminidase genes in the genetic background of A/Puerto Rico/8/34 (H1N1) virus. The mutants were selected with a panel of eight anti-HA monoclonal antibodies (MAbs), seven to A/Vietnam/1203/04 (H5N1) virus and one to A/Chicken/Pennsylvania/8125/83 (H5N2) virus, and the mutants' HA genes were sequenced. The amino acid changes suggested three MAb groups: four MAbs reacted with the complex epitope comprising parts of the antigenic site B of H3 HA and site Sa of H1 HA, two MAbs reacted with the epitope corresponding to the antigenic site A in H3 HA, and two MAbs displayed unusual behavior: each recognized amino acid changes at two widely separate antigenic sites. Five changes were detected in amino acid residues not previously reported as changed in H5 escape mutants, and four others had substitutions not previously described. The HA antigenic structure differs substantially between A/Vietnam/1203/04 (H5N1) virus and the low-pathogenic A/Mallard/Pennsylvania/10218/84 (H5N2) virus we previously characterized (N. V. Kaverin et al., J. Gen. Virol. 83:2497-2505, 2002). The hemagglutination inhibition reactions of the MAbs with recent highly pathogenic H5N1 viruses were consistent with the antigenic-site amino acid changes but not with clades and subclades based on H5 phylogenetic analysis. These results provide information on the recognition sites of the MAbs widely used to study H5N1 viruses and demonstrate the involvement of the HA antigenic sites in the evolution of highly pathogenic H5N1 viruses, findings that can be critical for characterizing pathogenesis and vaccine design.