Design of the phonocardiography appliance for coronary artery disease diagnosing and monitoring : business perspectives analysis of innovative medical technologies for cardiovascular diseases in Finland

The topic of this study is the application of modern medical technology to cardiovascular conditions. The main purpose of that research is to evaluate myocardium disorders from the versatile perspectives and propose the design of a socially-demanding and financially-efficient technological solution targeted to coronary artery disease (CAD) diagnosing and monitoring. Phonocardiography and audial CAD detection are discussed as innovative methods for personalized healthcare applications and based on that, digital product design is developed in the form of functional specification, wearable device model, iOS and WatchOS applications interface architecture. In addition to the diseases study, myocardium signals acquisition discussion and to device design itself, market research is conducted. It is focused on medical technologies segment in general and cardiological systems in particular. Finland and Nordic Europe are the major covered regions, while global trends are outlined to collect the vision on the general market tendency. Core assessment topics are medical technology product distribution models, investment potential and development barriers. The final result could be used as a foundation for further product development and as an overview or guidelines for businesses interested in healthcare Internet-of-Things and cardiological systems

Structural insights into thrombolytic activity of destabilase from medicinal leech

Destabilase from the medical leech Hirudo medicinalis belongs to the family of i-type lysozymes. It has two different enzymatic activities: microbial cell walls destruction (muramidase activity), and dissolution of the stabilized fibrin (isopeptidase activity). Both activities are known to be inhibited by sodium chloride at near physiological concentrations, but the structural basis remains unknown. Here we present two crystal structures of destabilase, including a 1.1 Å-resolution structure in complex with sodium ion. Our structures reveal the location of sodium ion between Glu34/Asp46 residues, which were previously recognized as a glycosidase active site. While sodium coordination with these amino acids may explain inhibition of the muramidase activity, its influence on previously suggested Ser49/Lys58 isopeptidase activity dyad is unclear. We revise the Ser49/Lys58 hypothesis and compare sequences of i-type lysozymes with confirmed destabilase activity. We suggest that the general base for the isopeptidase activity is His112 rather than Lys58. pKa calculations of these amino acids, assessed through the 1 μs molecular dynamics simulation, confirm the hypothesis. Our findings highlight the ambiguity of destabilase catalytic residues identification and build foundations for further research of structure–activity relationship of isopeptidase activity as well as structure-based protein design for potential anticoagulant drug development.</p

A fluorescent microspheres-based microfluidic test system for the detection of immunoglobulin G to SARS-CoV-2

Background: The pandemic of the new coronavirus infection, COVID-19, is currently ongoing in the world. Over the years, the pathogen, SARS-CoV-2, has undergone a series of mutational genome changes, which has led to the spread of various genetic variants of the virus. Meanwhile, the methods used to diagnose SARS-CoV-2, to establish the disease stage and to assess the immunity, are nonspecific to SARS-CoV-2 variants and time-consumable. Thus, the development of new methods for diagnosing COVID-19, as well as their implementation in practice, is currently an important direction. In particular, application of systems based on chemically modified fluorescent microspheres (with a multiplex assay for target protein molecules) opens great opportunities. Aim: development of a microfluidic diagnostic test system based on fluorescent microspheres for the specific detection of immunoglobulins G (IgG) to SARS-CoV-2. Methods: A collection of human serum samples was characterized using enzyme-linked immunosorbent assay (ELISA) and commercially available reagent kits. IgG to SARS-CoV-2 in the human serum were detected by the developed immunofluorescent method using microspheres containing the chemically immobilized RBD fragment of the SARS-CoV-2 (Kappa variant) viral S-protein. Results: The level of IgG in the blood serum of recovered volunteers was 9-300 times higher than that in apparently healthy volunteers, according to ELISA (p0.001). Conjugates of fluorescent microspheres with the RBD-fragment of the S-protein, capable of specifically binding IgG from the blood serum, have been obtained. The immune complexes formation was confirmed by the fluorescence microscopy data; the fluorescence intensity of secondary antibodies in the immune complexes formed on the surface of microspheres was proportional to the content of IgG (r 0.963). The test system had a good predictive value (AUC 70.3%). Conclusion: A test system has been developed, based on fluorescent microspheres containing the immobilized RBD fragment of the SARS-CoV-2 S-protein, for the immunofluorescent detection of IgG in the human blood serum. When testing the system on samples with different levels of IgG to SARS-CoV-2, its prognostic value was shown. The obtained results allow us to present the test system as a method to assess the level of immunoglobulins to SARS-CoV-2 in the human blood serum for the implementation in clinical practice. The test system can also be integrated into various microfluidic systems to create chips and devices for the point-of-care diagnostics

Internet of Things for personal healthcare. : Study of eHealth sector. Smart wearable design.

Technologies are not still and Internet of Things concept introduces a lot of new possibilities for inno-vation, new products and user applications. All devices become truly personal and medical sector is not an exclusion. Telemedicine is a new approach to diagnostic and treatment, while smart healthcare solutions provide the user an ultimate health control. The purpose of my study is to understand what eHealth sector is and to provide clear guidelines for business and IT specialists on how to enter the smart healthcare market. I analyzed the current market situation, made an audience research in Fin-land and prepared a whitepaper with basic rules, which can help to develop and design a valuable, secure product for personal use, which gives maximum profit for the company and ultimate usage convenience and experience for selected consumers. Following topics are covered in the paper: needs and requirements of healthcare IoT, regulations, adoption, IoT user experience, security and so on. I hope my work will help specialist from different fields to understand personal healthcare Internet of Things and to open new operating areas. Finally, I applied all collected theoretical knowledge and de-signed a smart insulin pump, what is an innovative and new product on today’s market

Review of the Problems of Diagnosis of Endopelvic Haemorrhage, Its Intensity, Volume, and Duration, and Treatment Methods of Circulatory Injuries and Surgical Hemostasis after Pelvic Fractures

Objective. The development of pelvic surgeries is now making new evolutionary jump for us to witness; this would be unimaginable without significant achievements in anesthesiology and new technologies of blood replacement. Methods. This overview presents analysis of 41 domestic and 20 foreign references sources that are devoted to the problematics of treating patients with fluid injuries of pelvis accompanied by retroperitoneal haemorrhage. Results. The following considers details on determination of endopelvic haemorrhage nature, its intensity, volume, and duration, as well as the treatment methods for circulatory injuries and surgical haemostasis. Conclusions. Energy of mechanical influence of traumatizing agent determines the damage levels (system disintegration) for pelvic ring, the bone core, and soft tissue mass. Diagnosis tactics and treatment of patients with disintegrating pelvic damage in the end are determined with volumes and intensity of haemorrhage as well as the character of related damage

Estimating some hydrophysical properties of soil using mathematical modeling

At substantiating land amelioration and land management designs, as well as during periods of operation and reconstruction of water facilities, information support plays an important role in relation to the hydrophysical properties of soil. Effective implementation of this support faces a number of challenges. Such problems include the very high laboriousness of carrying out the corresponding engineering surveys and laboratory studies. In this regard, the methods of indirect estimating the hydrophysical properties, the measurement of which requires considerable labor, are very in demand for land amelioration and land management practices. An equally acute problem is the problem of the functional representation of the coefficients of the Richards equation, which is widely used in engineering-hydrological calculations. The paper suggests: 1) the original method for assessment of the ratio of the values of the hydraulic conductivity function of soil to the moisture filtration coefficient using data from direct measurements of the water-retention capacity of soil carried out according to the standard procedure; 2) the mathematical model describing the hydrophysical properties of soil, and the system of functions with interpreted parameters that physically adequately describe the coefficients of the Richards equation. In carrying out the study, data on soils of different texture were used. A sufficiently low error in the dot approximation (fitting-procedure) of the experimental data confirms the physical adequacy of the proposed system that includes the functions describing the coefficients of the Richards equation

Estimating some hydrophysical properties of soil using mathematical modeling

At substantiating land amelioration and land management designs, as well as during periods of operation and reconstruction of water facilities, information support plays an important role in relation to the hydrophysical properties of soil. Effective implementation of this support faces a number of challenges. Such problems include the very high laboriousness of carrying out the corresponding engineering surveys and laboratory studies. In this regard, the methods of indirect estimating the hydrophysical properties, the measurement of which requires considerable labor, are very in demand for land amelioration and land management practices. An equally acute problem is the problem of the functional representation of the coefficients of the Richards equation, which is widely used in engineering-hydrological calculations. The paper suggests: 1) the original method for assessment of the ratio of the values of the hydraulic conductivity function of soil to the moisture filtration coefficient using data from direct measurements of the water-retention capacity of soil carried out according to the standard procedure; 2) the mathematical model describing the hydrophysical properties of soil, and the system of functions with interpreted parameters that physically adequately describe the coefficients of the Richards equation. In carrying out the study, data on soils of different texture were used. A sufficiently low error in the dot approximation (fitting-procedure) of the experimental data confirms the physical adequacy of the proposed system that includes the functions describing the coefficients of the Richards equation

Five models of hysteretic water-retention capacity and their comparison for sandy soil

A description of five mathematical models of the water-retention capacity of soil is given, taking into account the hysteresis phenomena. A computational experiment was carried out with these models using data on sandy soil. The experiment consisted of: (i) tuning of the models (parameter identification) by the method of dot-approximation of experimental data on the main drying and wetting branches of the hysteresis loop using an optimizing algorithm; (ii) the predictive calculation of the scanning branches of the hysteresis loop; (iii) a comparison of the errors in tuning results and the predictive calculation using the Williams-Kloot criteria. The commensurate and sufficiently low errors in the adjustment of the models have been achieved. The differences in the calculation of the scanning hysteresis branches are revealed. The practical significance of the mathematical models presented is to ensure the calculation of precision irrigation rates. The application of such rates in irrigation farming will help to prevent excess moisture from flowing beyond the root layer of the soil under the influence of gravity and, thus, to minimize the losses (unproductive consumption) of irrigation water, fertilizers, meliorants and plant protection products, and also reduce the risk of groundwater contamination with agrochemicals and eutrophication of water bodies

Five models of hysteretic water-retention capacity and their comparison for sandy soil

A description of five mathematical models of the water-retention capacity of soil is given, taking into account the hysteresis phenomena. A computational experiment was carried out with these models using data on sandy soil. The experiment consisted of: (i) tuning of the models (parameter identification) by the method of dot-approximation of experimental data on the main drying and wetting branches of the hysteresis loop using an optimizing algorithm; (ii) the predictive calculation of the scanning branches of the hysteresis loop; (iii) a comparison of the errors in tuning results and the predictive calculation using the Williams-Kloot criteria. The commensurate and sufficiently low errors in the adjustment of the models have been achieved. The differences in the calculation of the scanning hysteresis branches are revealed. The practical significance of the mathematical models presented is to ensure the calculation of precision irrigation rates. The application of such rates in irrigation farming will help to prevent excess moisture from flowing beyond the root layer of the soil under the influence of gravity and, thus, to minimize the losses (unproductive consumption) of irrigation water, fertilizers, meliorants and plant protection products, and also reduce the risk of groundwater contamination with agrochemicals and eutrophication of water bodies

Microarray Profiling of Vaccination-Induced Antibody Responses to SARS-CoV-2 Variants of Interest and Concern

Mutations in surface proteins enable emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to escape a substantial fraction of neutralizing antibodies and may thus weaken vaccine-driven immunity. To compare available vaccines and justify revaccination, rapid evaluation of antibody (Ab) responses to currently circulating SARS-CoV-2 variants of interest (VOI) and concern (VOC) is needed. Here, we developed a multiplex protein microarray-based system for rapid profiling of anti-SARS-CoV-2 Ab levels in human sera. The microarray system was validated using sera samples from SARS-CoV-2-free donors and those diagnosed with COVID-19 based on PCR and enzyme immunoassays. Microarray-based profiling of vaccinated donors revealed a substantial difference in anti-VOC Ab levels elicited by the replication-deficient adenovirus vector-base (Sputnik V) and whole-virion (CoviVac Russia COVID-19) vaccines. Whole-virion vaccine-induced Abs showed minor but statistically significant cross-reactivity with the human blood coagulation factor 1 (fibrinogen) and thrombin. However, their effects on blood clotting were negligible, according to thrombin time tests, providing evidence against the concept of pronounced cross-reactivity-related side effects of the vaccine. Importantly, all samples were collected in the pre-Omicron period but showed noticeable responses to the receptor-binding domain (RBD) of the Omicron spike protein. Thus, using the new express Ab-profiling system, we confirmed the inter-variant cross-reactivity of the anti-SARS-CoV-2 Abs and demonstrated the relative potency of the vaccines against new VOCs