Search

The aim: to study the indices of stress-deforming state of biomechanical system «bone — hybrid anchor» in proximal humerus fractures. Material and Methods. The study of anchorage stiffness in juxta-articular fracture (type 11A3 by AO/ASIF) through applying three load types: axial (200 N), transverse (30 N) and torsional (5 N*m) was conducted followed by CAD modeling in SolidWorks and the analysis of stress-deforming state of the system «bone — anchor». Results. While studying the stability of «bone — anchor» system it was found that a new device for proximal humerus fracture ostheosynthesis under the applied loads do not decompose with maximal translocations of bone fragments and maximums of equivalent stress being present under torsional load and comprise 1.6 mm. and 152 Mpa respectively. Conclusion. The application of hybrid devices for juxta-articular fractures of humerus allows carrying out minimally traumatic anchorage with the following early functionality of the injured segment.

The aim: to identify the efficiency of the improved technology of treatment of tibia marginal defects with the use of granular composite osteoplastic materials during external fixation of fragments. Material and Methods. The observation group was made up of 12 patients with the consequences of lower extremity traumas who had undergone osteosyn-thesis of fractures by an external fixation device with defect alloplasty We used clinical and ray-tracing testing methods and also standardized system of assessment of outcomes of bone fractures and their consequences to control the processes of restoration of bone structure integrity. Results. According to the standardized system of assessment of outcomes in 12-18 months in the course of the rehabilitation measures degree of restoration of anatomic functional indices was 92±5%. Bone density made up 91,3±0,54 HU (p

Keratins 6, 16, and 17 occupy unique positions within the keratin family. These proteins are not commonly found in the healthy, intact epidermis, but their expression increases in response to damage, inflammation, and hereditary skin conditions, as well as cancerous cell transformations and tumor growth. As a result, there is an active investigation into the potential use of these proteins as biomarkers for different pathologies. Recent studies have revealed the role of these keratins in regulating keratinocyte migration, proliferation, and growth, and more recently, their nuclear functions, including their role in maintaining nuclear structure and responding to DNA damage, have also been identified. This review aims to summarize the latest research on keratins 6, 16, and 17, their regulation in the epidermis, and their potential use as biomarkers in various skin conditions.

The pre-mRNA life cycle requires intron processing; yet, how intron-processing defects influence splicing and gene expression is unclear. Here, we find that TTDN1/MPLKIP, which is encoded by a gene implicated in non-photosensitive trichothiodystrophy (NP-TTD), functionally links intron lariat processing to spliceosomal function. The conserved TTDN1 C-terminal region directly binds lariat debranching enzyme DBR1, whereas its N-terminal intrinsically disordered region (IDR) binds the intron-binding complex (IBC). TTDN1 loss, or a mutated IDR, causes significant intron lariat accumulation, as well as splicing and gene expression defects, mirroring phenotypes observed in NP-TTD patient cells. A Ttdn1-deficient mouse model recapitulates intron-processing defects and certain neurodevelopmental phenotypes seen in NP-TTD. Fusing DBR1 to the TTDN1 IDR is sufficient to recruit DBR1 to the IBC and circumvents the functional requirement for TTDN1. Collectively, our findings link RNA lariat processing with splicing outcomes by revealing the molecular function of TTDN1.

Introduction. The article discusses the current state of the possibilities to improve the efficiency of construction processes by using fibre-reinforced concrete in the construction of transport and utility tunnels, as well as other critical building structures. The authors present foreign experience with widespread use of fibre-reinforced concrete in transport construction, as well as few such cases for domestic practice. The inconsistency of domestic experience with the modern state of art has been noted. The main blockers in the development of the issue are under consideration, the theoretical approach and practical application are presented. Materials and methods. The principal aspects of the current approach to the quality indicators of fibre-reinforced concrete and the classification principles of fibre-reinforced concrete based on quality criteria, which are the basis for the normalization of material characteristics, are described. The continuity of domestic and European regulatory documents is shown. Results. Illustrated examples of the possibilities of an optimization approach to the selection of structural solutions in the design of transport construction facilities used in international practice are described. Conclusion. The argumentation in favor of technology development is shown. This opens up possibilities for significant cost reduction justified by a scientific approach. In conclusion, the authors provide recommendations on the general application of the promising material in the domestic practice

BACKGROUND: Time in range (TIR) is a promising indicator of glycemic control used for evaluation of continuous glucose monitoring (CGM) for patients with diabetes mellitus (DM). The current problem is the assessment and prediction of TIR for patients who use self-monitoring of blood glucose (SМBG) corresponding low CGM availability for the majority of diabetic patients.AIM: To develop a predictive model of TIR for patients with T1DM based on data of the experimental mobile application.MATERIALS AND METHODS: An analysis of 1253 professional CGM profiles of patients with T1DM was performed. On the base of included records, TIR(CGM) was calculated and training models of 7-point SMBG profiles were generated. SMBG profiles’re loaded into the developed experimental mobile application that calculated standard glycemic control parameters. The dataset was divided into main and test samples (80 and 20%). For the main sample, the following methods’re used to develop predictive models: simple linear regression (SLR), multiple linear regression (MLR), artificial neural network (ANN). The effectiveness of the developed models was assessed on the test sample with the calculation of the mean absolute error (MAE), the root mean square error (RMSE).RESULTS: The 568 CGM profiles’re included in the study. TIR in the main group (n=454) — 45 [33; 65]%, in the test group (n=114) — 43 [33; 58]%. The most significant predictors of the regression models were the derived TIR (dTIR), p

The aim: is to compare short-term results of home-based and outpatient programs of physical therapy among patients with frozen shoulder and concomitant thoracic myofascial pain syndrome. Materials and methods. The study involved 80 patients. The range of motion in the shoulder joint affected by capsulitis was assessed. A numerical pain scale was used to assess pain sensations when pressing on trigger points. Functional limitations in the shoulder were measured by means of the Oxford Shoulder Score (before and 1.5 months after the end of the physical therapy). Participants were divided into two groups: home-based group (HG) and outpatient group (ОG). All the patients were consulted by a physical therapist. ОG patients received end-range mobilization with the assistance of a physical therapist 5 times a week to improve shoulder joint mobility. Most of ОG participants received 15 procedures (3 weeks). Patients HG performed therapeutic exercises without any assistance at home. (twice a day, 3 weeks). In terms of trigger points therapy, the patients performed ischemic compression without any assistance. Results. Patients of both groups demonstrated positive dynamics of the studied indicators. Comparison of the short-term results of the therapy according to range of motion and pain showed better indicators in the ОG. Comparison of the initial results of the groups in Oxford Shoulder Score items did not reveal any significant differences. Total score was 18.2±6.5 points in ОG and 17.6±7.5 points in HG (p=0.715). Me (25%; 75%) values were 17.5 (12.5; 23.8) and 18 (13; 23.5) points, respectively. Comparison of the final results of the groups in Oxford Shoulder Score items revealed significant differences. Total score was 47 (47; 48) points in ОG and 33 (31; 35.75) points in HG (p

Abstract The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4–6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in the open configuration. Remarkably, Polθi binding to the Polθ-pol:DNA/DNA closed complex traps the polymerase on DNA for more than forty minutes which elucidates the inhibitory mechanism of action. These data reveal a unique small-molecule DNA polymerase:DNA trapping mechanism that induces synthetic lethality in HR-deficient cells and potentiates the activity of PARPi.

The paper describes an algorithm for the design of axial and radial-axial type turbines. The algorithm is based on using mathematical models of various levels of complexity – from 1D to 3D. Flow path geometry is described by means of analytical methods of profiling using a limited number of parameters. 3D turbulent flow model is realised in the program complex IPMFlow, developed based on the earlier codes FlowER and FlowER-U. Examples of developed or modernized turbines for differentpurpose power machines are presented. They are: an expansion turbine, ORC turbine and cogeneration mediumpressure turbine.

The article deals with new treatment technique in fractures of shin bones. It combines ideal reduction of damaged bone with reposition device without transition of transosseous elements through muscular masses, adequate fixation of bone fragments and change of biomechanical efforts in apparatus according to reparative osteogenesis phases. It is performed due to application of external fixation apparatus

Approximately 50% of tumors carry mutations in TP53; thus, evaluation of the features of mutant p53 is crucial to understanding the mechanisms underlying cell transformation and tumor progression. HaCaT keratinocytes represent a valuable model for research in this area since they are considered normal, although they bear two gain-of-function mutations in TP53. In the present study, transcriptomic and proteomic profiling were employed to examine the functions of mutant p53 and to investigate the impact of its complete abolishment. Our findings indicate that CRISPR-mediated TP53 knockout results in significant changes at the transcriptomic and proteomic levels. The knockout of TP53 significantly increased the migration rate and altered the expression of genes associated with invasion, migration, and EMT but suppressed the epidermal differentiation program. These outcomes suggest that, despite being dysfunctional, p53 may still possess oncosuppressive functions. However, despite being considered normal keratinocytes, HaCaT cells exhibit oncogenic properties.

Background. Pancreatic head cancer ranks 6–7th among oncologic diseases and 4–5th among causes of mortality, with only 5% of patients achieving 5-year survival rate to date. Despite the successes of modern diagnostics and surgical treatment, the problem of early detection, staging of oncologic process and, as a consequence, combined treatment of pancreatic head cancer remains actual.Objective: increasing the accuracy of diagnostics and estimation of resectability of the pancreatic head cancer on the basis of the complex use of the radiation methods of investigation with pancreaticoduodenal zone 3D-reconstructions.Material and methods. The study included 93 patients (44 (47.31%) males and 49 (52.69%) females) with complicated pancreatoduodenal masses treated from 2019 to 2022 at the Surgical Department of the City Mariinsky Hospital. The patients’ age varied from 44 to 90 years, the mean age was 67±0.74 years. All patients underwent magnetic resonance imaging (MRI) on an Ingenia MR tomograph (Philips Medical Systems, Netherlands) with a magnetic field induction of 3 Tesla. The native examination of the abdomen and retroperitoneum, supplemented with MR-cholangiopancreatography protocol, and dynamic contrast enhancement with data collection in arterial, portal, and delayed phases were carried out. T2-weighted images were then performed using turbospin-echo technology, including fat-suppressed images, to evaluate structural changes and the presence of fluid in fascial spaces. Patients also underwent endoscopic ultrasound of the pancreaticoduodenal zone using the push and pull method, and abdominal multislice computed tomography (MSCT). To build 3D models, we used free 3D-slicer and Mimics programs, which allowed to build semi-automatic model for further evaluation of anatomo-topographic relations.Results. MSCT 3D modeling revealed tumor invasion into the superior mesenteric vein in 6 (23.06%) patients, whereas MRI models showed tumor invasion in 4 (15.38%) patients, intraoperatively the results were confirmed in 5 patients (19.23%). According to both MSCT and MRI modeling data, the invasion of the ventral trunk occurred in 1 (5.2%) case, which was confirmed intraoperatively. Inferior vena cava invasion on MSCT and MRI models was detected in 3 (11.54%) patients, whereas intraoperatively – in 4 (15.38%) patients. The MSCT and MRI 3D models coincided with the data on invasion of the ventral trunk in 1 (3.85%) patient and the superior mesenteric artery in 2 (7.69%) patients, which was fully confirmed intraoperatively.Conclusion. 3D modeling on the basis of MRI and MSCT studies is an informative method in preoperative staging of pancreatic head cancer and its resectability. This method allows to objectively determine the localization and prevalence of the tumor process on adjacent anatomical structures, as well as visually demonstrate the metastatic lesion of regional lymph nodes. By the parameters of diagnostic efficiency, 3D models are maximally close to the intraoperative picture, which allows planning both the volume and the course of surgical intervention.

The thermal scheme of a power generating plant with a remote heat exchanger operating according to the Brayton cycle with energy recuperation is considered. It is assumed that the plant will work on non-certified (cheap) biofuel. It is shown that, in contrast to the usual Brayton cycle, in the cycle with energy recuperation, the greatest influence on the thermal efficiency is the heating temperature of the working medium and the internal efficiency of the main components of the plant, such as the compressor and the turbine. Also, in contrast to the usual Brayton cycle, a higher efficiency of the plant is achieved with smaller degrees of pressure reduction (increase) in the turbine (compressor). It was established that even at a relatively low temperature of the working medium heating (500 ºC), with high efficiency of the compressor and turbine, it is possible to achieve good characteristics of the power plant as a whole. At a temperature of up to 850 ºC, a thermal efficiency of 40% is achieved, but in this case the cost of materials and production increases. For a final conclusion about the possibility of using the proposed plant and its efficiency, it is necessary to conduct additional studies, in particular, of its main elements, such as a compressor, turbine, heat exchanger and others.

Aim. Evaluation of comorbid pathology in SARS-CoV-2 infected in cancer practice as a predictor of severe outcomes. Testing the COVID-19 risk assessment tool in oncology (CORONET), to predict the likely severity of COVID-19 course in cancer patients on inpatient treatment. Materials and methods. A retrospective analysis of 173 cancer patient disease stories was conducted. The study was conducted as part of the program of the World-Class Research Center “Digital Biodesine and Personalized Health Care” of the University of Sechenov, with participation in the ESMO-CoCARE Register project. Based on the ESMO COVID-19 and CAncerREgistry (ESMO-CoCARE) registry, taking into account the entered our patient sample (n=173), a COVID-19 risk assessment tool in oncology (CORONET) was developed. Results. Cancer patients with comorbid pathology have been shown to have an increased risk of COVID-19 course of the disease from this sample by CORONET (mean conclusion score CORONET 2.44 pointsseverity). Prognosis of probable severity of outcomes in cancer patients infected with SARS-CoV-2 depends on associated diseases. The presence of a history of ≥3 comorbid pathologies in COVID-19 patients was detected in 106 people (61.27%). 15 patients were included in the risk of severe course. Retrospective analysis obtained actual confirmation of the prognosis of severe course of the disease in this group followed by death in all these patients (71.42% of all deaths). Indicators such as low albumin levels, high levels of C-reactive protein and neutrophils showed high prognostic significance of the likely severity of coronavirus infection in cancer patients on inpatient treatment for COVID-19. The mortality rate of patients admitted with COVID-19 and cancer was 12.14%. Conclusion. The most informative predictors of severe outcomes in COVID-19 in inpatient cancer patients to assess the prognosis of disease severity are: number of comorbidities, age, NEWS2 scale, ECOG patient activity status, albumin level, C-reactive protein level and absolute neutrophil level. The benefits gained in the use of the online decision support tool CORONET are considered convincing not only during the decision-making phase of hospitalization, but also in cancer patients on inpatient treatment.

Abstract Background Mesenchymal stromal cells (MSCs) have regenerative and immunomodulatory properties, making them suitable for cell therapy. Toll-like receptors (TLRs) in MSCs respond to viral load by secreting immunosuppressive or proinflammatory molecules. The expression of anti-inflammatory molecules in MSCs can be altered by the concentration and duration of exposure to the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)). This study aimed to optimize the preconditioning of MSCs with poly(I:C) to increase immunosuppressive effects and to identify MSCs with activated TLR3 (prMSCs). Methods Flow cytometry and histochemical staining were used to analyze MSCs for immunophenotype and differentiation potential. MSCs were exposed to poly(I:C) at 1 and 10 μg/mL for 1, 3, and 24 h, followed by determination of the expression of IDO1, WARS1, PD-L1, TSG-6, and PTGES2 and PGE2 secretion. MSCs and prMSCs were cocultured with intact (J−) and activated (J+) Jurkat T cells. The proportion of proliferating and apoptotic J+ and J− cells, IL-10 secretion, and IL-2 production after cocultivation with MSCs and prMSCs were measured. Liquid chromatography–mass spectrometry and bioinformatics analysis identified proteins linked to TLR3 activation in MSCs. Results Poly(I:C) at 10 μg/mL during a 3-h incubation caused the highest expression of immunosuppression markers in MSCs. Activation of prMSCs caused a 18% decrease in proliferation and a one-third increase in apoptotic J+ cells compared to intact MSCs. Cocultures of prMSCs and Jurkat cells had increased IL-10 and decreased IL-2 in the conditioned medium. A proteomic study of MSCs and prMSCs identified 53 proteins with altered expression. Filtering the dataset with Gene Ontology and Reactome Pathway revealed that poly(I:C)-induced proteins activate the antiviral response. Protein‒protein interactions by String in prMSCs revealed that the antiviral response and IFN I signaling circuits were more active than in native MSCs. prMSCs expressed more cell adhesion proteins (ICAM-I and Galectin-3), PARP14, PSMB8, USP18, and GBP4, which may explain their anti-inflammatory effects on Jurkat cells. Conclusions TLR3 activation in MSCs is dependent on exposure time and poly(I:C) concentration. The maximum expression of immunosuppressive molecules was observed with 10 µg/mL poly(I:C) for 3-h preconditioning. This priming protocol for MSCs enhances the immunosuppressive effects of prMSCs on T cells.

Abstract [68Ga]Ga-PSMA-11 PET has become the standard imaging modality for biochemically recurrent (BCR) prostate cancer (PCa). However, its prognostic value in assessing response at this stage remains uncertain. The study aimed to assess the prognostic significance of radiographic patient-level patterns of progression derived from lesion-level biomarker quantitation in metastatic disease sites. A total of 138 BCR PCa patients with both baseline and follow-up [68Ga]Ga-PSMA-11 PET scans were included in this analysis. Tumour response was quantified at the lesion level using commonly used quantitative parameters (SUVmean, SUVmax, SUVpeak, volume), and patients were classified as systemic, mixed, or no-progression based on these response classifications. A total of 328 matched lesions between baseline and follow-up scans were analysed. The results showed that systemic progressors had a significantly higher risk of death than patients with no progression with SUVmean demonstrating the highest prognostic value (HR = 5.70, 95% CI = 2.63–12.37, p

Microbial communities of terrestrial mud volcanoes are involved in aerobic and anaerobic methane oxidation, but the biological mechanisms of these processes are still understudied. We have investigated the taxonomic composition, rates of methane oxidation, and metabolic potential of microbial communities in five mud volcanoes of the Taman Peninsula, Russia. Methane oxidation rates measured by the radiotracer technique varied from 2.0 to 460 nmol CH4 cm−3 day−1 in different mud samples. This is the first measurement of high activity of microbial methane oxidation in terrestrial mud volcanos. 16S rRNA gene amplicon sequencing has shown that Bacteria accounted for 65–99% of prokaryotic diversity in all samples. The most abundant phyla were Pseudomonadota, Desulfobacterota, and Halobacterota. A total of 32 prokaryotic genera, which include methanotrophs, sulfur or iron reducers, and facultative anaerobes with broad metabolic capabilities, were detected in relative abundance >5%. The most highly represented genus of aerobic methanotrophs was Methyloprofundus reaching 36%. The most numerous group of anaerobic methanotrophs was ANME-2a-b (Ca. Methanocomedenaceae), identified in 60% of the samples and attaining relative abundance of 54%. The analysis of the metagenome-assembled genomes of a community with high methane oxidation rate indicates the importance of CO2 fixation, Fe(III) and nitrate reduction, and sulfide oxidation. This study expands current knowledge on the occurrence, distribution, and activity of microorganisms associated with methane cycle in terrestrial mud volcanoes.