Highly Adherent Antimicrobial Coatings for Orthopedic Implants

Fracture-related infections (FRIs) are the most devasting sort of complications associated with fracture fixation devices, as they lead to patients’ morbidity, prolonged hospitalization, amputations, and even death.External fixators additionally suffer from pin site infections (PSIs), which initiate at the skin entry points of the skin-metallic pin interface present in the external fixation of the damaged bones, often causing deep tissue infection and osteomyelitis. Small percutaneous pins, commonly known as Kirschner wires (K-wires), are used to treat complex fractures and deformities.They are drilled inside the diseased bone for the healing period and are left protruding outside the skin for fixation adjustments and easy removal. Metal surface of the K-wires, however, provides an anchor for the pathogens to adhere and migrate underneath the skin toward the bone, where they can form biofilms and become resistant to oral and intravenous antibiotics. While the incidence rate of PSIs has been reported to reach 100%, there is still limited literature regarding the prevention of PSIs and the overall lack of pin site-specific research.Despite the significant improvements in post-surgical aseptic technique, there is no consensus on either optimal antimicrobial dressing for the post-operative period or burying K-wires under the closed skin wound. Drug-releasing surface coatings of the implants is the recently emerged trend to address clinicallyimportant issues such as prophylaxis of microbial infections and reduction of inflammatory response. Some orthopedic implants, however, are subjected to large shear forces, which remove or damage any weakly adhered physiosorbed coatings. Hence, little progress has been made on drug-releasing coatings for those implants. Our research, therefore, aims to fill that gap on the drug-eluting orthopedic implants and the modeling of their abrasion-resistance properties. In this study, we have developed two types of highly adhesive drug-releasing coating: the synthetic Poly(glycidyl methacrylate) (PGMA)-based polymeric brush and the natural chitosan coatings. Derived from the shells of crustaceans, chitosan is a linear polysaccharide molecule that is generally recognized as safe by FDA and is currently pending approval for drug delivery applications. Furthermore, chitosan has been shown to possess antimicrobial activity against a wide variety of microorganisms, produce films with good mechanical properties, and stimulate new bone formation.The synthetic (PGMA)-based copolymer, on the other hand, is a branched molecule that consists of three individual monomers: glycidyl methacrylate (GMA) - a cross-linkable monomer with epoxy group which can form stable permanent network; a hydrophilic oligoethylene glycol methacrylate (OEGMA), which provides compatibilization with water; and a hydrophobiclauryl methacrylate (LMA), which provides amphiphilic balance to the resulting macromolecule. We hypothesized that our developed drug-loaded coatings would retain antimicrobial properties after drilling into compact bone or its mimetic and would be superior to the plain drug and the drug-loaded commercial Poly(DL-lactide) (PLA) coatings. The objective of this study was to validate this platform technology for drug-eluting orthopedic implants with specific focus on K-wires because of the high incidence of infections for these devices. In the first part of the dissertation, we prepared and characterized two types of coatings, chitosan-based and PGMA-based. By varying matrix composition parameters of the polymer and drug loading we identified the optimal formulations capable of resisting shear forces during K-wire drilling in vitro. In the second part of the dissertation, we characterized antimicrobial efficacy of the best-performing coatings before and after the drilling. The findings of this aim helped us to choose the optimal coating for the pilot in vivo study. We conducted the animal study which confirmed the effectiveness of the applied highly adherent antimicrobial coating

Structured data abstractions and interpretable latent representations for single-cell multimodal genomics

Single-cell multimodal genomics involves simultaneous measurement of multiple types of molecular data, such as gene expression, epigenetic marks and protein abundance, in individual cells. This allows for a comprehensive and nuanced understanding of the molecular basis of cellular identity and function. The large volume of data generated by single-cell multimodal genomics experiments requires specialised methods and tools for handling, storing, and analysing it. This work provides contributions on multiple levels. First, it introduces a single-cell multimodal data standard — MuData — designed to facilitate the handling, storage and exchange of multimodal data. MuData provides interfaces that enable transparent access to multimodal annotations as well as data from individual modalities. This data structure has formed the foundation for the multimodal integration framework, which enables complex and composable workflows that can be naturally integrated with existing omics-specific analysis approaches. Joint analysis of multimodal data can be performed using integration methods. In order to enable integration of single-cell data, an improved multi-omics factor analysis model (MOFA+) has been designed and implemented building on the canonical dimensionality reduction approach for multi-omics integration. Inferring later factors that explain variation across multiple modalities of the data, MOFA+ enables the modelling of latent factors with cell group-specific patterns of activity. MOFA+ model has been implemented as part of the respective multi-omics integration framework, and its utility has been extended by software solutions that facilitate interactive model exploration and interpretation. The newly improved model for multi-omics integration of single cells has been applied to the study of gene expression signatures upon targeted gene activation. In a dataset featuring targeted activation of candidate regulators of zygotic genome activation (ZGA) — a crucial transcriptional event in early embryonic development, — modelling expression of both coding and non-coding loci with MOFA+ allowed to rank genes by their potency to activate a ZGA-like transcriptional response. With identification of Patz1, Dppa2 and Smarca5 as potent inducers of ZGA-like transcription in mouse embryonic stem cells, these findings have contributed to the understanding of molecular mechanisms behind ZGA and laid the foundation for future research of ZGA in vivo. In summary, this work’s contributions include the development of data handling and integration methods as well as new biological insights that arose from applying these methods to studying gene expression regulation in early development. This highlights how single-cell multimodal genomics can aid to generate valuable insights into complex biological systems

Static Load Induced Liquefaction, Steels Corners Road Embankment Failure

A simple, roadway widening became significantly more expensive when geologic conditions conspired to complicate the project. The widening was to be accomplished by the construction of a 25-foot wide and 15-foot high embankment. The embankment was located adjacent to a “wetland” area and pond. Fill placement begin and a height of 7 feet was reached when operations ceased for the week. Work began two days later. A 400-foot long scarp formed and the fill “moved” nearly 4 feet vertically and 1-foot laterally. An initial suspicion of settlement due to compression of peat was dismissed when no organic deposits were found beneath the embankment. The exploration encountered glacial outwash deposits consisting of alternating layers of thick, relatively loose, hydrostatically-charged sand confined between thin, dense clay strata. Consolidation settlement analysis could not account for the magnitude of vertical or the lateral component of the movement. We concluded that the embankment construction caused the liquefaction of the sand layers beneath the fill; effectively reducing the shear strength to zero. Slope stability analysis confirmed the only means of producing the failure was to introduce positive pore pressure into the sand deposits. The resulting shallow, circular failure surface was a near-perfect match of the head scarp and toe bulge observed in the wetland at the edge of the pond. To increase pore pressure, three criteria must be met; the availability of water with sufficient head to completely saturate and “charge” the strata, the prevention of free drainage, and the increase of soil strain through dynamic or static loading. The buried glacial valley, the presence of the ‘kettle’ lake, and rapid construction of the embankment fulfilled these criteria

Labor and youth: contradictions, problems and solutions — philosophical view

В статье рассматриваются проблемные точки существования современной молодежи в труде в условиях постмодернистского социокультурного сдвига. Обосновывается возможность формирования в молодежной среде трудового человека нового типа способного к преодолению наличествующих противоречий в системе молодежного труда.The author considers the problem points of the existence modern youth in work in the conditions of postmodern socio-cultural shift. Substantiates the possibility of formation among the youth a new type working man, capable of overcoming the contradictions in the system youth labor

Civil War in Ukraine: Scientific Approaches and the Factor of the Cossacks

Introduction. The events in Ukraine in 2013-2014 contributed to the manifestation of the Ukrainian political crisis, which led to the secession of the Crimean Peninsula, the Donetsk and Luhansk People’s Republics. The new Ukrainian authorities, realizing the impossibility of returning the Crimea, launched a military operation against the DPR and LPR, the so-called “ATO”. The general civil confrontation between Kiev on the one hand and Donetsk and Luhansk on the other hand led to the beginning of the civil war in Ukraine, the fact of which is not recognized by the Ukrainian authorities, but is presented as “Russian aggression”. Methods. Through institutional analysis, the study identifies approaches to understanding the factor of the civil war in Ukraine. Analysis. The participants of the armed confrontation, both on the part of Ukraine, and on the part of the DPR and LPR, are Ukrainian citizens. The fact that there are a significant number of Russian citizens among the militia, primarily from among the Cossacks, is due to the historical unity of the lands of the pre-revolutionary Region of the Don Army, socio-cultural and blood-related factors. The participation of the Cossacks in the conflict is of particular importance in the context of Ukraine’s positioning itself as a “Cossack country”. An important place in the understanding of the military confrontation is occupied by the transnationalization of political elites for the post-Soviet space, which acts as an impulse for the unity of the population of the former USSR. In a civil war, there is no boundary dividing the parties on civilizational, ethnic and linguistic grounds. But at the same time, some authors highlight the factor of regional identity. Results. Approaches to the definition of the civil war in Ukraine are revealed. The reluctance of the perception of the concept of “civil war” by the Ukrainian authorities is determined. The assessment of the further development of the civil war in the country is given

The Influence of Foreign States on the Activities of Extremist Organisations in the South of Russia

Introduction. The problem of the spread of extremist organizations’ activities in the South of Russia is intensified due to the increasing role of international actors and the influence of neighboring States. Extremist groups are included in the sphere of interests of countries with high level of institutional instability that have unresolved territorial administrative problems and also major terrorist organizations such as the ‘Islamic State’ (ISIL) prohibited on the territory of the Russian Federation. Methods. The author applies an institutional method to determine the role of international influence on the development of extremist organizations in the South of Russia. Analysis. Despite the decline in its activity, the ISIL continues to be among the priority threats to international security. The Russian Federation has successfully conducted anti-terrorist operation in Syria, while the ISIL operates in Iraq and other regions of the world. Its area of interest includes Russia, since the ISIL units exist on the territory of the Caucasus region and the Crimean Peninsula. At the same time, the territory of the Rostov region and the Republic of Crimea are subjected to the influence of the Ukrainian geo-strategic interests. The Ukrainian authorities act with territorial claims to the Russian Federation on a number of border regions as well as organize sabotage operations and support marginal movements. The so-called ‘Circassian question’ continues to be significant for the South of Russia. In the context of the present research, the author poses the problem of considering the interaction of neighboring countries and extremist organizations in the Russian border regions. The institutional research approaches allow determining the main “point of tension” in the southern border area, and to identify the main actors influencing the extremist organization. Results. The results of the work give conclusions about the main directions of foreign States’ influence on the regions of the South of Russia and counteraction to them by the security authorities

Military Service of the Cossacks in the Security System of the South of Russia (On the Example of Rostov Region)

Introduction. Modern Russian Cossacks, having undergone the process of revival and institutionalization, are now incorporated into the system of state and other services of the Russian Federation. Given the pre-revolutionary status of the Cossacks as a military class of the Russian Empire, Ministry of Defense of the Russian Federation, beginning from the 1990s, has a particular interest in attracting the descendants of the Cossacks and members of Cossack societies to military service. Methods. Through the institutional analysis, the study assesses the role of the Cossacks in military service and security in the South of Russia. Analysis. In order to incorporate the Cossacks into the system of military service in the Russian Federation, a number of normative legal acts have been adopted that allow the Cossacks to serve in Cossack units with traditional Cossack names, to use Cossack insignia on military uniforms. As part of the implementation of the Strategy of the state policy of the Russian Federation in relation to the Russian Cossacks until 2020, regional plans for its implementation, Cossack societies are actively involved in the preparation of pre-conscription youth, interact with military commissariats. Recently, pilot projects have been launched to create specialized Cossack territorial defense companies. At a high level, the participation of the Cossacks in ensuring public order during important international events has been evaluated: the XXII Winter Olympic Games in Sochi, the World Cup 2018. Results. The need to expand the participation of the Cossacks in the military service of the Russian Federation by increasing the number of territorial defense companies, opening Cossack cadet corps, forming the role of the Cossacks as a guarantor of stabilization of interethnic relations of the South of Russia