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Chronic kidney disease is detected in 8–15% of the world’s population. Along with fibrotic changes, it can lead to a complete loss of organ function. Therefore, a better understanding of the onset of the pathological process is required. To address this issue, we examined the interaction between mast cells (MCs) and cells in fibrous and intact regions, focusing on the role of MC proteases such as tryptase, chymase, and carboxypeptidase A3 (CPA3). MCs appear to be involved in the development of inflammatory and fibrotic changes through the targeted secretion of tryptase, chymase, and CPA3 to the vascular endothelium, nephron epithelium, interstitial cells, and components of intercellular substances. Protease-based phenotyping of renal MCs showed that tryptase-positive MCs were the most common phenotype at all anatomic sites. The infiltration of MC in different anatomic sites of the kidney with an associated release of protease content was accompanied by a loss of contact between the epithelium and the basement membrane, indicating the active participation of MCs in the formation and development of fibrogenic niches in the kidney. These findings may contribute to the development of novel strategies for the treatment of tubulointerstitial fibrosis.

Preparation of a redox-frustrated high-energy-density energetic material is achieved by gentle protolysis of Mn[N(SiMe3)2]2with the perchlorate salt of the tetrazolamide [H2NtBuMeTz]ClO4(Tz = tetrazole), yielding the Mn6N6hexagonal prismatic cluster, Mn6(μ3-NTztBuMe)6(ClO4)6. Quantum mechanics-based molecular dynamics simulations of the decomposition of this molecule predict that magnetic ordering of the d5Mn2+ions influences the pathway and rates of decomposition, suggesting that the initiation of decomposition of the bulk material might be significantly retarded by an applied magnetic field. We report here experimental tests of the prediction showing that the presence of a 0.5 T magnetic field modulates the ignition onset temperature by +10.4 ± 3.9 °C (from 414 ± 4 °C), demonstrating the first example of a magnetically modulated explosive.

Objective: Previously, low-dose radiation therapy was used for pneumonia treatment. We aimed to investigate the safety and effectiveness of carbon nanoparticles labeled with Technetium isotope (99mTc) in a form of ultradispersed aerosol in combination with standard COVID-19 therapy. The study was a randomized phase 1 and phase 2 clinical trial of low-dose radionuclide inhalation therapy for patients with COVID-19 related pneumonia.Methods: We enrolled 47 patients with confirmed COVID-19 infection and early laboratory signs of cytokine storm and randomized them into the Treatment and Control groups. We analyzed blood parameters reflecting the COVID-19 severity and inflammatory response.Results: Low-dose 99mTc-labeled inhalation showed a minimal accumulation of radionuclide in lungs in healthy volunteers. We observed no significant differences between the groups before treatment in WBC-count, D-dimer, CRP, Ferritin or LDH levels. We found that Ferritin and LDH levels significantly raised after the 7th day follow-up only in the Control group (p < 0.0001 and p = 0.0005, respectively), while mean values of the same indicators did not change in patients in the Treatment group after the radionuclide treatment. D-dimer values also lowered in the radionuclide treated group, however, this effect was not statistically significant. Furthermore, we observed a significant decrease in CD19+ cell counts in patients of the radionuclide-treated group.Conclusion: Inhalation low-dose radionuclide therapy of 99mTc aerosol affects the major prognostic indicators of COVID-19- related pneumonia restraining inflammatory response. Overall, we identified no evidence of major adverse events in the group receiving radionuclide.

This article presents a review of the methods of determining spleen size in sonography, computed tomography, and magnetic resonance imaging. The review aims to summarize the data on the methods of estimating the linear dimensions of the spleen and splenic volume and describe the physiological variability of spleen size depending on sex, age, and different physiological conditions. We systematized the methods used for measuring the spleen and presented them in the form of a table, analyzed the results of previous studies, and compared the accuracy of different methods of calculating the splenic volume using a variety of diagnostic methods.

Coherent twin boundaries (CTBs) with the lowest interfacial energy provide a strong phonon-CTB scattering source to suppress the lattice thermal conductivity needed for thermoelectric properties, but the impact on mechanical properties of PbTe remains unexplored. We construct nanotwinned structures with Pb- or Te-terminated CTB (Pb- or Te-CTB) along (111) plane and employ molecular dynamics simulations to examine structural evolution. We find that Pb-CTBs weaken ionic Pb-Te bonds to generate an easy dislocation source at CTBs. Due to nucleation and motion of partial dislocations on each Pb-CTB plane driven by shear load, Pb-CTBs gradually migrate to Te-CTBs, which is accompanied by breaking and re-forming of Pb-Te bonds. This “catching bond” maintains structural integrity while dramatically enhancing deformability of nanotwinned PbTe. Dislocations move from Te-CTBs toward twin lamellae, resulting in the structural slippage and fracture. These findings provide a theoretical strategy to improve the ductility of PbTe-based semiconductors through TB engineering.

Type-I clathrate Ba8Au6Ge40, possessing an interesting structure stacked by polyhedrons, is a potential “phonon-glass, electron-crystal” thermoelectric material. However, the mechanical properties of Ba8Au6Ge40vital for industrial applications have not been clarified. Here, we report the first density functional theory calculations of the intrinsic mechanical properties of thermoelectric clathrate Ba8Au6Ge40. Among the different loading directions, the {110}/⟨001⟩ shearing and ⟨110⟩ tension are the weakest, with strengths of 4.51 and 6.64 GPa, respectively. Under {110}/⟨001⟩ shearing, the Ge–Ge bonds undergo significant stretching and twisting, leading to a severe distortion of the tetrakaidecahedral cage, giving rise to the fast softening of the flank Au–Ge bonds. At a strain of 0.2655, the Au–Ge bonds suddenly break, resulting in the collapse of the cage and the failure of the material. Under a ⟨110⟩ tension, the stretching of the Ge–Ge bonds keeps accelerating the softening of the Au–Ge bonds in the top/bottom hexagons, which releases the stress and disables the structure. The Au–Ge bonds are more rigid, contributing two-thirds of the structural deformation resistance. This work provides a new insight to understand the failure mechanisms of type-I clathrates with varied framework constitutions, which should help inform the design of robust thermoelectric clathrate materials.

This article focuses on the notion of an ambiguous category such as the "transport contract". The difficulties in defining this concept are due to the fact that there is ambiguity in related concepts such as "carriage", "transport service" and "transport process". Purpose: To form a scientific understanding of the transport contract and the criteria to distinguish this concept from related contractual constructions. Methods: systematic approach, methods of comparison, description, interpretation; theoretical methods of formal and dialectical logic. Particular scientific methods were used: comparative-legal and the method of legal norms interpretation. Results: Analysis of the positions of scientists and current civil legislation has shown that the transport contract is characterized by specific subject composition, connection with the transportation process and purposefulness. Conclusions: It is necessary to distinguish transport contracts from other contracts, in which one of the parties is a transport organization, in particular from the contract of lease of vehicles with crew. Despite the assertion of many scholars that the concept of a transport contract can only be used for scientific purposes, it is argued that the concept can also be used for practical purposes, for example, in the process of codification.

Fracture mechanics is a fundamental topic to materials science. Fracture toughness, in particular, is a material property of great technological importance for device design. The relatively low fracture toughness of many semiconductor materials, including electronic and energy materials, handicaps their use in applications involving large external stresses. Here, it is shown that quantum-mechanical density functional theory calculations of ideal strength, in conjunction with an integral stress-displacement method, can be used to estimate the fracture energy needed to calculate fracture toughness. Using the fracture energy associated with the weakest crystallographic direction provides an estimation for the lower-limit of the fracture toughness of a material. The lower-limit values are in good agreement with experimental single crystal measurements across several orders-of-magnitude of fracture toughness. Furthermore, the proposed methodology is useful for benchmarking experimental measurements of fracture toughness in polycrystalline materials and can serve as a starting point for the construction of more detailed fracture models and the computational design of new materials and devices.

Purpose: to develop a procedure for registering changes, notifying users about changes made, unifying software as a medical device based on artificial intelligence technologies (SaMD-AI) changes, as well as requirements for testing and inspections—quality control before and after making changes. Methods: The main types of changes, divided into two groups—major and minor. Major changes imply a subsequent change of a SaMD-AI version to improve efficiency and safety, to change the functionality, and to ensure the processing of new data types. Minor changes imply those that SaMD-AI developers can make due to errors in the program code. Three types of SaMD-AI testings are proposed to use: functional testing, calibration testing or control, and technical testing. Results: The presented approaches for validation SaMD-AI changes were introduced. The unified requirements for the request for changes and forms of their submission made this procedure understandable for SaMD-AI developers, and also adjusted the workload for the Experiment experts who checked all the changes made to SaMD-AI. Conclusion: This article discusses the need to control changes in the module of SaMD-AI, as innovative products influencing medical decision making. It justifies the need to control a module operation of SaMD-AI after making changes. To streamline and optimize the necessary and sufficient control procedures, a systematization of possible changes in SaMD-AI and testing methods was carried out.

Energetic materials (EMs) are central to construction, space exploration, and defense, but over the past 100 years, their capabilities have improved only minimally as they approach the CHNO energetic ceiling, the maximum energy density possible for EMs based on molecular carbon–hydrogen–nitrogen–oxygen compounds. To breach this ceiling, we experimentally explored redox-frustrated hybrid energetic materials (RFH EMs) in which metal atoms covalently connect a strongly reducing fuel ligand (e.g., tetrazole) to a strong oxidizer (e.g., ClO4). In this Article, we examine the reaction mechanisms involved in the thermal decomposition of an RFH EM, [Mn(Me2TzN)(ClO4]4(3, Tz = tetrazole). We use quantum-mechanical molecular reaction dynamics simulations to uncover the atomistic reaction mechanisms underlying this decomposition. We discover a novel initiation mechanism involving oxygen atom transfer from perchlorate to manganese, generating energy that promotes the fission of tetrazole into chemically stable species such as diazomethane, diazenes, triazenes, and methyl azides, which further undergo exothermic decomposition to finally form stable N2, H2O, CO, CO2, Mn-based clusters, and additional incompletely combusted products.

Of the two stable forms of graphite, hexagonal and rhombohedral, the former is more common and has been studied extensively. The latter is less stable, which has so far precluded its detailed investigation, despite many theoretical predictions about the abundance of exotic interaction-induced physics1–6. Advances in van der Waals heterostructure technology7have now allowed us to make high-quality rhombohedral graphite films up to 50 graphene layers thick and study their transport properties. Here we show that the bulk electronic states in such rhombohedral graphite are gapped8and, at low temperatures, electron transport is dominated by surface states. Because of their proposed topological nature, the surface states are of sufficiently high quality to observe the quantum Hall effect, whereby rhombohedral graphite exhibits phase transitions between a gapless semimetallic phase and a gapped quantum spin Hall phase with giant Berry curvature. We find that an energy gap can also be opened in the surface states by breaking their inversion symmetry by applying a perpendicular electric field. Moreover, in rhombohedral graphite thinner than four nanometres, a gap is present even without an external electric field. This spontaneous gap opening shows pronounced hysteresis and other signatures characteristic of electronic phase separation, which we attribute to emergence of strongly correlated electronic surface states.

The aim of the study was to compare the rates of nutrients consumption in children and adolescents with gastroesophageal reflux disease (GERD) compared to the control group without the disease. Based on symptom evaluation and esophageal pH-impedance recordings patients were allocated on to GERD and control groups. All patients underwent esophagogastroscopy. Levels of nutrients consumption were assessed with the use of food frequency questionnaire in the regard to the presence of the disease, esophagitis, and zscore body mass index (BMI). Data of 219 children and adolescents were available for the final analysis. Risks to have GERD were higher in groups with obesity (risk ratio 1.2 [95% confidence interval 0.8–1.7]) and excessive weight (1.1 [0.9–1.4]). Energy values of the rations and amount of fat consumption were higher in the GERD group compared to the control when rations were compared according to zscore BMI. In contrast to nonerosive form of GERD, patients with erosive esophagitis consumed more protein (percentage deviation from the recommended daily allowance Me [25%;75%]): 14.3 (11.07; 19.1) % versus 8.5 (6.71; 14.1) %, total fat 36.8 (12.5; 75.5) % versus 16.9 (10.1; 17.9) %, and less polyunsaturated fats -54.3 (-73.4; -47.7) % versus -45.6 (-56.2; -33.1) %, P?

α-MgAgSb based thermoelectric (TE) device attracts much attention for its commercial application because it shows an extremely high conversion efficiency of ∼8.5% under a temperature difference of 225 K. However, the mechanical behavior of α-MgAgSb is another serious consideration for its engineering applications. Here, we apply density functional theory (DFT) simulations to examine the intrinsic mechanical properties of all three MgAgSb phases, including elastic properties, shear-stress – shear-strain relationships, deformation and failure mechanism under ideal shear and biaxial shear conditions. We find that the ideal shear strength of α-MgAgSb is 3.25 GPa along the most plausible (100)<010> slip system. This strength is higher than that of β-MgAgSb (0.80 GPa) and lower than that of γ-MgAgSb (3.43 GPa). The failure of α-MgAgSb arises from the stretching and breakage of MgSb bond α-MgAgSb under pure shear load, while it arises from the softening of MgAg bond and the breakage of AgSb bond under biaxial shear load. This suggests that the deformation mechanism changes significantly under different loading conditions.

Engineering grain boundaries (GBs) are effective in tuning the thermoelectric (TE) properties of TE materials, but the role of GB on mechanical properties, which is important for their commercial applications, remains unexplored. In this paper, we apply ab initio method to examine the ideal shear strength and failure mechanism of GBs in TE oxide BiCuSeO. We find that the ideal shear strength of the GB is much lower than that of the ideal single crystal. The atomic rearrangements accommodating the lattice and neighbor structure mismatch between different grains leads to the much weaker GB stiffness compared with grains. Failure of the GBs arises from either the distortion of the Cu–Se layers or the relative slip between Bi–O and Cu–Se layers. This work is crucial to illustrate the deformation of GBs, laying the basis for the development and design of mechanically robust polycrystalline TE materials.

Herein, the possibility of creating a noncascade intersubband midinfrared injection laser based on HgCdTe with a minimum number of quantum wells is analyzed. An error‐tolerant laser structure with three quantum wells that is insensitive to the variations in the quantum well thickness is proposed. The calculations predict a modal gain of 35 cm−1at the wavelength of approximately 9.2 μm at 77 K and the operating temperature up to 125 K. A scheme of HgCdTe‐based noncascade intersubband midinfrared injection laser is proposed. The proposed design has only one tunnel‐coupled transition, which is tuned by the applied electric field. This design is tolerant to errors in thicknesses of the quantum wells and the barriers.

A decade of intense research on two-dimensional (2D) atomic crystals has revealed that their properties can differ greatly from those of the parent compound. These differences are governed by changes in the band structure due to quantum confinement and are most profound if the underlying lattice symmetry changes. Here we report a high-quality 2D electron gas in few-layer InSe encapsulated in hexagonal boron nitride under an inert atmosphere. Carrier mobilities are found to exceed 103cm2V−1s−1and 104cm2V−1s−1at room and liquid-helium temperatures, respectively, allowing the observation of the fully developed quantum Hall effect. The conduction electrons occupy a single 2D subband and have a small effective mass. Photoluminescence spectroscopy reveals that the bandgap increases by more than 0.5 eV with decreasing the thickness from bulk to bilayer InSe. The band-edge optical response vanishes in monolayer InSe, which is attributed to the monolayer's mirror-plane symmetry. Encapsulated 2D InSe expands the family of graphene-like semiconductors and, in terms of quality, is competitive with atomically thin dichalcogenides and black phosphorus.

Our objective was to evaluate the safety and clinical efficacy of autologous M2 macrophage transplantation in nonacute stroke patients. We also evaluated whether the intrathecal administration of macrophages influences the production of cytokines by peripheral blood cells and whether the levels of cytokines correlate with stroke severity and responsiveness to cell therapy. In this study, 13 patients (12 males and 1 female with a median age of 63 years) diagnosed with ischemic (n= 10) or hemorrhagic (n= 3) stroke were subjected to cell transplantation therapy (study group). On average, 21.9 × 106autologous M2 macrophages were injected intrathecally. Thirteen matched case-control stroke patients who did not receive cell therapy comprised the control group. We did not observe any serious adverse events (i.e., intrahospital mortality, neurological worsening, and seizures) related to the cell injection. One patient in the study group and two patients in the control group died during the 6-month follow-up period due to recurrent stroke. In the study group, the NIHSS score decreased from 11 to 6 (p= 0.007) in 6 months after the therapy, whereas the patients in the control group showed a less pronounced neurological improvement (the NIHSS score decreased from 11 to 8, p= 0.07). The obvious positive response (the improvement of the NIHSS score ≥3) in the study group was observed in 75% versus 18% in the control group (pFET= 0.03). M2 cell introduction did not significantly affect the production of various cytokines. Nevertheless, pretreated levels of IL-8, IL-10, and IL-4 correlated with stroke severity. Moreover, responder patients had lower spontaneous production of IL-10, FGF-β, PDGF, VEGF, and higher stimulation indexes of IL-1β, TNF-α, IFN-γ, and IL-6 than nonresponders. These findings suggest that the intrathecal administration of autologous M2 cells in stroke patients is safe and leads to a better neurological recovery, which could be mediated through the immunomodulatory activity of M2 macrophages.

Ruoff and co-workers recently demonstrated low-temperature (1193 K) homoepitaxial diamond growth from liquid gallium solvent. To develop an atomistic mechanism for diamond growth underlying this remarkable demonstration, we carried out density functional theory-based molecular dynamics (DFT-MD) simulations to examine the mechanism of single-crystal diamond growth on various low-index crystallographic diamond surfaces (100), (110), and (111) in liquid Ga with CH4. We find that carbon linear chains form in liquid Ga and then react with the growing diamond surface, leading first to the formation of carbon rings on the surface and then initiation of diamond growth. Our simulations find faster growth on the (110) surface than on the (100) or (111) surfaces, suggesting the (110) surface as a plausible growth surface in liquid Ga. For (110) surface growth, we predict the optimum growth temperature to be ∼1300 K, arising from a balance between the kinetics of forming carbon chains dissolved in Ga and the stability of carbon rings on the growing surface. We find that the rate-determining step for diamond growth is dehydrogenation of the growing hydrogenated (110) surface of diamond. Inspired by the recent experimental studies by Ruoff and co-workers demonstrating that Si accelerates diamond growth in Ga, we show that addition of Si into liquid Ga significantly increases the rate of dehydrogenating the growing surface. Extrapolating from the DFT-MD predicted rates at 2800 to 3500 K, we predict the growth rate at the experimental growth temperature of 1193 K, leading to rates in reasonable agreement with the experiment. These fundamental mechanisms should provide guidance in optimizing low-temperature diamond growth.

While the complex 7 × 7 structure that arises upon annealing the Si(111) surface is well-known, the mechanism underlying this unusual surface reconstruction has remained a mystery. Here, we report molecular dynamics simulations using a machine-learning force field for Si to investigate the Si(111)-7 × 7 surface reconstruction from the melt. We find that there are two possible pathways for the formation of the 7 × 7 structure. The first path arises from the growth of a faulted half domain from the metastable 5 × 5 phase to the final 7 × 7 structure, while the second path involves the direct formation of the 7 × 7 reconstruction. Both pathways involve the creation of dimers and bridged five-membered rings, followed by the formation of additional dimers and the stabilization of the triangular halves of the unit cell. The corner hole is formed from the joining of several five-member rings. The insertion of atoms below the adatoms to form a dumbbell configuration involves extra atom diffusion or rearrangement during the evolution of triangular halves and dimer formation along the unit cell boundary. Our findings may provide insights for manipulating the surface structure by introducing other atomic species.

In this study, we used quantum mechanics (QM) to investigate steam reforming of methane on Ni-alloy catalyst surfaces and to examine the effect of anode material modifications on the catalytic processes in a solid oxide fuel cell (SOFC). The conventional Ni anode suffers from coking, coarsening, and sulfur poisoning because of the decomposition of hydrocarbon fuels, Ni particle agglomeration at high operating temperature, and impurities contained in fuels. Ni-electrode surface modification, such as alloying Ni with other metals (e.g., Fe and Cu), is probably the most practical and promising way of developing SOFC anodes tolerant to coking and sulfur poisoning. According to experimental data, Ni4Fe shows a good catalytic performance and excellent long-term stability as an SOFC anode catalyst. We have performed QM calculations of segregation energy for various surface structures of five-layer Ni4M slabs (M = Co, Fe, and Mn) and found that Ni atoms show segregation preference for the surface layer and the most favorable Ni4M surface structure has two M atoms in the 2nd layer and one M atom in the 3rd and in the 4th layer (the numbering starts from the bottom layer). This structure was used for our further QM calculations of binding energies for CHx, C, and H. We find that the Ni4M(111) surfaces bind CHxspecies weaker (by 1–10 kcal/mol) than pure Ni, and the binding energy of C is always ∼10 kcal/mol lower for the Ni4M alloys compared to pure Ni. This is consistent with improved catalytic characteristics of certain Ni-based alloys compared to pure Ni obtained in experiment. Reaction energy barriers for methane decomposition on the Ni4M(111) catalyst surfaces were calculated as well. On the basis of these results, the rate-determining step for the methane decomposition was found to be the CH → C + H reaction. Our results predict that Ni4Fe and Ni4Mn have both better activity and better coking resistance and can be considered as candidates for an SOFC anode catalyst suitable for the CH4fuel reforming.

We report large-yield production of graphene flakes on glass by anodic bonding. Under optimum conditions, we counted several tens of flakes with lateral size around 20–30 μm and a few tens of flakes with larger size. About 60–70% of the flakes have a negligible D peak. We show that it is possible to easily transfer the flakes by the wedging technique. The transfer on silicon does not damage graphene and lowers the doping. The charge mobility of the transferred flakes on silicon is on the order of 6000 cm2/V s (at a carrier concentration of 1012cm–2), which is typical for devices prepared on this substrate with exfoliated graphene.

We consider the Brown–Ravenhall model of a relativistic atom with Nelectrons and a nucleus of charge Zand prove the existence of an infinite number of discrete eigenvalues for N⩽ Z. As an intermediate result we prove a HVZ-type theorem for these systems.

ABSTRACTRNA silencing is a natural defense mechanism against genetic stress factors, including viruses. A mutant hordeivirus (Barley stripe mosaic virus[BSMV]) lacking the ?bgene was confined to inoculated leaves in Nicotiana benthamiana, but systemic infection was observed in transgenic N. benthamianaexpressing the potyviral silencing suppressor protein HCpro, suggesting that the ?b protein may be a long-distance movement factor and have antisilencing activity. This was shown for ?b proteins of both BSMV and Poa semilatent virus(PSLV), a related hordeivirus. Besides the functions in RNA silencing suppression, ?b and HCpro had analogous effects on symptoms induced by the hordeiviruses. Severe BSMV-induced symptoms were correlated with high HCpro concentrations in the HCpro-transgenic plants, and substitution of the ?b cistron of BSMV with that of PSLV led to greatly increased symptom severity and an altered pattern of viral gene expression. The efficient systemic infection with the chimera was followed by the development of dark green islands (localized recovery from infection) in leaves and exemption of new developing leaves from infection. Recovery and the accumulation of short RNAs diagnostic of RNA silencing in the recovered tissues in wild-type N. benthamianawere suppressed in HCpro-transgenic plants. These results provide evidence that potyviral HCpro and hordeivirus ?b proteins contribute to systemic viral infection, symptom severity, and RNA silencing suppression. HCpro's ability to suppress the recovery of plants from viral infection emphasizes recovery as a manifestation of RNA silencing.

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Faba bean necrotic yellows virus (FBNYV) has a multicomponent circular ssDNA genome. In addition to a previously described genome component (C1) coding for a replicase-associated protein (Rep), five further components (C2 to C6) have now been identified. Each of the six components is about 1 kb in size, contains one major open reading frame (ORF) in the virion sense with a TATA box and polyadenylation signal, and has a noncoding region containing a highly conserved sequence possibly forming a stem–loop structure. Similar to C1, C2 encodes another putative Rep of 33.1 kDa, which is closely related to the Rep of banana bunchy top virus (BBTV). Based on bacterial expression and immunoblot analysis, the ORF of C5 encodes the capsid protein (CP) with a deduced molecular mass of 19 kDa. The FBNYV CP shares the highest amino acid (aa) identity (56.2%) with that of subterranean clover stunt virus (SCSV). The ORF of C4 potentially codes for a hydrophobic protein which appears to be structurally and functionally similar to the BBTV-C4 and SCSV-C1 proteins. No protein sequence similarities were found in databases for the C3 and C6 ORFs of FBNYV. FBNYV is clearly distinct from any known virus but is taxonomically related to BBTV and SCSV.

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Background and aimsA non-interventional study (NIS) was performed by Bionorica LLC company to collect data on the use of the herbal medicinal product (HMP) Canephron®N in routine paediatric practice in Russia.MethodsChildren of 1–17 years of age with confirmed diagnoses of urinary system disease and who were prescribed treatment with the HMP participated in the study at 26 polyclinics and out-patient departments. Exclusion criteria comprised hypersensitivity to any components of HMP, unsigned informed consent form, gastric ulcer and duodenal ulcer in the acute stage, participation in another clinical trial simultaneously or during 3 months before enrolment. Observational period included study treatment and follow-up period and was limited to a maximum of 6 weeks. Key parameters were prescribed indications, prescribed/actual treatment regimen, duration of treatment, co-medications, global assessments of HMP effectiveness and tolerability by physician and patient/parent, analysis of Adverse Events/Adverse Drug Reactions (AE/ADR). The NIS was approved by the local ethics committees and conducted with site monitoring by a contract research organisation.Results636 children aged 1–17 years were enrolled and 634 (470 girls) of them comprised Safety Set: 61 in the age of 1–2 years, 227 in 2–5 years, 234 in 6–11 years and 112 in 12–17 years. The main indications for HMP prescription were urinary tract infection (34.1%), pyelonephritis (30.0%), dysmetabolic nephropathy (18.9%), cystitis (11.5%), urolithiasis (4.1%) and nephritis (3.6%). HMP was prescribed for treatment in 307 (48.3%) patients, for prophylaxis in 157 (24.7%) and both for treatment and prophylaxis in 172 (27%) of patients. HMP in oral solution was prescribed in 66.4% of patients and tablets in 33.6%. Any concomitant medication was reported in 61.8% of patients. Effectiveness assessments by physician and patient/parent at visit 2 were ‘good’ and ‘very good’ in 88.2% and 87.9% and at visit 3 in 89.1% and 89.1%, correspondingly. Tolerability assessments as ‘good’ and ‘very good’ at visits 2 and 3 varied from 98.1% to 99.2%. In total, 100 AEs were registered and 5 AEs were evaluated as ADRs (including 1 serious ADR (renal colic)).ConclusionsEffectiveness and good tolerability of the HMP in the treatment and prophylaxis of urinary diseases in children of 1–17 years was confirmed. According to registered safety data, the HMP can be considered safe and well tolerated for children of the studied age.