Search

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has caused considerable stress and anxiety in the general population, especially among students. The objective of this study was to determine the stress and anxiety levels among medical rehabilitation students induced by distance education during the COVID-19 pandemic. Methodology: The sample for this prospective cross-sectional study included 96 students pursuing the medical rehabilitation undergraduate degree at the Faculty of Medicine, University of Novi Sad, Serbia. All respondents took part in an online survey created on the Google Forms platform and accessed via the Facebook social network. The questionnaire included a sociodemographic section, the perceived stress scale (PSS), and the worry about online learning scale (WOLS). All data were analyzed using the IBM SPSS version 25. Results: The study involved 96 students with an average age of 21.97 ± 1.55 years, 72.9% of whom were female. The total stress reported by the students during the COVID-19 pandemic was higher in females than in males (21.75 [SD = 7.50] vs. 17.84 [SD = 8.58]; p < 0.05). Younger students were more susceptible to experiencing stress during the pandemic (rho = -0.217, p < 0.05). Moreover, 57.3% of students suffered from moderate stress, while the WOLS scores indicated that distance education induced a high level of discomfort in this cohort (3.8 [IQR = 1.6]). Conclusions: Medical rehabilitation students showed a moderate level of stress and a high level of concern about distance education. This stress was more prevalent among younger students and females.

Background/Aim. Cerebral palsy (CP) etiology is multi-factorial and heterogeneous, manifesting as damage to the developing brain. The associated risk factors can arise in the prenatal, perinatal, or postnatal period. The aim of this study was to determine the risk factors for CP and examine the associations between CP type, gestational age, and perinatal risk factors. Methods. The study sample comprised 206 children with CP. Pertinent data were collected from medical records and included participants? gestational age at birth, medical history, and CP clinical characteristics. Risk factors were divided according to the timing of brain injury into prenatal, perinatal, and neonatal. Results. Hormonally maintained pregnancy (55.3%), twin pregnancy (28.9%), vaginal bleeding after the 20th week of gestation (21.1%), threatened abortion in the first half of pregnancy (13.2%), and maternal infection (10.5%) were identified as the main prenatal risk factors for CP. Prematurity (54.5%) was the leading perinatal risk factor, followed by low birthweight (50.8%), Apgar score < 7 (41.7%), assisted delivery (41.4%), and breech presentation (13.5%). Respiratory distress syndrome (16%), need for treatment in the Neonatal Intensive Care Unit (22.3%), assisted ventilation (18.4%), hypoxic-ischemic encephalopathy (11.2%), and neonatal convulsions (5.8%) were identified as the leading neonatal risk factors for CP. A statistically significant difference was found in the total number of perinatal risk factors in relation to gestational age (p < 0.001) and CP type (p = 0.006). Perinatal risk factors were most prevalent in preterm infants and children affected by the CP of spastic bilateral type. A statistically significant difference was noted in the distribution of CP types de-pending on the gestational age (p < 0.001). In particular, spastic bilateral CP type was most prevalent in the group of preterm-born children. Conclusion. CP is characterized by heterogeneous risk factors and is a result of interaction among multiple risk factors.

The biocompatibility and effects on cells' bioactivity of developed pharmaceuticals are crucial properties, required to permit their safe delivery. Nanogel matrices offer a promising role in emerging pharmaceutics; however, it is crucial that they and their excipients do not demonstrate detrimental effects on the cells to which they interact. This study investigated the use of Teflon and the secondary bile acid deoxycholic acid in the formation of novel nanogel matrices. Each has properties which may be of benefit for the nanogels created and their use in the pharmaceutical industry. Rheological parameters and scanning electron microscopy studies were conducted. In order to assess the developed nanogels' impacts on cellular bioactivity, studies using Seahorse assays were conducted on three cell types, hepatic, muscle and pancreatic beta cells. Results demonstrated the addition of Teflon did not alter the morphological characteristics of resulting nanogels or the metabolic profiles of the cell lines. Interestingly, pancreatic beta cells highlighted the potential of Teflon to exert a protective profile from mitochondrial damage. Overall, the developed nanogels showed potentially promising profiles in certain studies conducted which may lead to future research.

Aim: Major challenges to islet transplantation in Type 1 diabetes include host-inflammation, which results in failure to maintain survival and functions of transplanted islets. Therefore, this study investigated the applications of encapsulating the bile acid ursodeoxycholic acid (UDCA) with transplanted islets within improved nano-gel systems for Type 1 diabetes treatment. Materials & methods: Islets were harvested from healthy mice, encapsulated using UDCA-nano gel and transplanted into the diabetic mice, while the control group was transplanted encapsulated islets without UDCA. The two groups' survival plot, blood glucose, and inflammation and bile acid profiles were analyzed. Results & conclusion: UDCA-nano gel enhanced survival, glycemia and normalized bile acids' profile, which suggests improved islets functions and potential adjunct treatment for insulin therapy.

Hearing loss is a worldwide epidemic, with approximately 1.5 billion people currently struggling with hearing-related conditions. Currently, the most wildly used and effective treatments for hearing loss are primarily focus on the use of hearing aids and cochlear implants. However, these have many limitations, highlighting the importance of developing a pharmacological solution that may be used to overcome barriers associated with such devices. Due to the challenges of delivering therapeutic agents to the inner ear, bile acids are being explored as potential drug excipients and permeation enhancers. This review, therefore, aims to explore the pathophysiology of hearing loss, the challenges in treatment and the manners in which bile acids could potentially aid in overcoming these challenges.

Tumor necrosis factor alpha (TNF-α), which enhances osteoclast activity and bone resorption, is one of the key inflammation mediators in rheumatoid arthritis (RA). The aim of this study was to assess the influence of yearlong TNF-α inhibitor application on bone metabolism. The study sample comprised 50 female patients with RA. Analyses involved the osteodensitometry measurements obtained using a “Lunar” type apparatus and the following biochemical markers from serum: procollagen type 1 N-terminal propeptide (P1NP), beta crosslaps C-terminal telopeptide of collagen type I (b-CTX) by ECLIA method, total and ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone and vitamin D. Analyses revealed changes in bone mineral density (BMD) at L1–L4 and the femoral neck, with the difference in mean BMD (g/cm2) not exceeding the threshold of statistical significance (p = 0.180; p = 0.502). Upon completion of 12-month therapy, a significant increase (p < 0.001) in P1NP was observed relative to b-CTX, with mean total calcium and phosphorus values following a decreasing trend, while vitamin D levels increased. These results suggest that yearlong application of TNF inhibitors has the capacity to positively impact bone metabolism, as indicated by an increase in bone-forming markers and relatively stable BMD (g/cm2).

BACKGROUND: The presence of low back pain in nurses is becoming increasingly prominent and it has significant impact both on the individual as well as on the community. OBJECTIVE: The aim of this study was to determine the prevalence of low back pain among practicing nurses. METHODS: The research has been conducted in five health care institutions in the area of Vojvodina. Data were collected using the Nordic Musculoskeletal Questionnaire (NMQ). RESULTS: Five hundred and twelve nurses participated in this study. Most of the participants (93.95%) indicated that they experienced discomfort or pain in the lower back in the last 12 months. Due to low back pain, 61.95% of participants had reduced working abilities and 76.09% of participants have never taken time off from work. CONCLUSIONS: Due to low back pain nurses have a reduced working capacity, but they nevertheless rarely seek medical help or the change of the work place. The implementation of better ergonomic approach and adequate organization of work could reduce the occurrence of low back pain.

Emergency Medicine does not represent a simple collection of various medical conditions, but rather an urgent approach to life threatening conditions. This urgent approach progresses as fast as the science in medicine does. Modern protocols for treatment of injured and ill patients are introduced, demanding more and more knowledge and skills as well as more modern equipment and wider spectrum of drugs. However, innovations are not followed by changes within the lists of medications set by National Health Insurance Fund of Serbia (NHIFS). Paper describes drugs necessary for adequate pre-hospital treatment that are not available to the physicians due to administrative barriers. On one hand, there are drugs from B list that are necessary for treatment, and are approved for use by NHIFS at hospital level only. The use of any of these drugs at pre-hospital level may lead to severe penalties to the physician in case of complications or adverse reactions in a patient following the treatment. On the other hand, there are drugs from D list which are also necessary for the urgent treatment of patients with life threatening conditions, according to latest recommendations. These drugs may be applied at pre-hospital level, but their procurement is complicated due to NHIFS regulations and that's why some of them may rarely be used (Propafenone and Magnesium sulfate). We particularly emphasize that one of the most effective drugs for the conversion of heart rhythm, Adenosine (6 mg/ml and 10mg/ml ampoule), is not registered in the Republic of Serbia and therefore cannot be used at pre-hospital level. Through these exclusive administrative barriers adequate treatment is rendered impossible while the system of urgent treatment of patients with life threatening conditions at pre-hospital level is degraded.

Bile acids present important roles in the human body and changes in their pool can be used as markers for various liver pathologies. In part, the unconjugated or conjugated, secondary or primary nature of bile acids accounts for their various effect as ligands in addition to their functional effects in modulating inflammatory responses and cellular survivability. With no documented baseline levels of bile acids or their receptors in the inner ear system, some hydrophilic bile acids have been used successfully as a treatment to resolve drug induced cell damage or to ameliorate hearing loss. This review, presents both hydrophilic and hydrophobic human bile acids along with their tissue-specific ligand effects in modulating cellular integrity, bringing in consideration the possible effects and therapeutic applicability of bile acids to the inner ear tissue.

Clinical laboratory practice represents an essential part of clinical decision-making, as it influences 60-70% of medical decisions at all levels of health care. Results of biochemical laboratory tests (BLTs) have a key role in establishment of adequate diagnosis as well as in evaluation of treatment progress and outcome. The prevalence of drug-laboratory test interactions (DLTIs) is up to 43% of patients who had laboratory results influenced by drugs. Unrecognized DLTIs may lead to misinterpreted BLTs results, incorrect or delayed diagnosis, extra costs for unnecessary additional tests or inadequate therapy, as all may cause false clinical decisions. The significance of timely and adequate recognition of DLTIs is to prevent common clinical consequences such as incorrectly interpreted test results, delayed or non-treated condition due to erroneous diagnosis or unnecessary extra tests or therapy. Medical professionals should be educated that it is essential to obtain patient data about medications especially for the drugs used in the last 10 days before biological material collection. Our mini-review aims to provide a comprehensive overview of the current state in this important domain of medical biochemistry with detailed analysis of the effect of drugs on BLTs and to give detailed information to medical specialists.

Introduction: Although pharmacogenetics and pharmacogenomics have been at the forefront of research aimed at finding novel personalized therapies, the focus of research has recently extended to the potential of intestinal microbiota to affect drug efficacy. Complex interplay of gut microbiota with bile acids may have significant repercussions on drug pharmacokinetics. However, far too little attention has been paid to the potential implication of gut microbiota and bile acids in simvastatin response which is characterized by large interindividual variations.The Aim: In order to gain more insight into the underlying mechanism and its contribution in assessing the clinical outcome, the aim of our study was to examine simvastatin bioaccumulation and biotransformation in probiotic bacteria and the effect of bile acids on simvastatin bioaccumulation in in vitro conditions.Materials and methods: Samples with simvastatin, probiotic bacteria and three different bile acids were incubated at anaerobic conditions at 37°C for 24 h. Extracellular and intracellular medium samples were collected and prepared for the LC-MS analysis at predetermined time points (0 min, 15 min, 1 h, 2 h, 4 h, 6 h, 24 h). The concentrations of simvastatin were analyzed by LC-MS/MS. Potential biotransformation pathways were analyzed using a bioinformatics approach in correlation with experimental assay.Results: During the incubation, simvastatin was transported into bacteria cells leading to a drug bioaccumulation over the time, which was augmented upon addition of bile acids after 24 h. A decrease of total drug level during the incubation indicates that the drug is partly biotransformed by bacterial enzymes. According to the results of bioinformatics analysis, the lactone ring is the most susceptible to metabolic changes and the most likely reactions include ester hydrolysis followed by hydroxylation.Conclusion: Results of our study reveal that bioaccumulation and biotransformation of simvastatin by intestinal bacteria might be the underlying mechanisms of altered simvastatin bioavailability and therapeutic effect. Since this study is based only on selected bacterial strains in vitro, further more in-depth research is needed in order to elicit completely the contribution of complex drug-microbiota-bile acids interactions to overall clinical response of simvastatin which could ultimately lead to novel approaches for the personalized lipid-lowering therapy.

Infestation of the road-killed hedgehogs (Erinaceus roumanicus) with Ixodes ticks in some parts of Upper Thracian Plain (Bulgaria) was investigated. A total of 5 tick species from 3 genera were identified.

Microencapsulation of formulation designs further expands the field and offers the potential for use in developing bioartificial organs via cell encapsulation. Combining formulation design and encapsulation requires ideal excipients to be determined. In terms of cell encapsulation, an environment which allows growth and functionality is paramount to ensuring cell survival and incorporation into a bioartificial organ. Hence, excipients are examined for both individual properties and benefits, and compatibility with encapsulated active materials. Polymers are commonly used in microencapsulation, offering protection from the immune system. Bile acids are emerging as a tool to enhance delivery, both biologically and pharmaceutically. Therefore, this review will focus on bile acids and polymers in formulation design via microencapsulation, in the field of bioartificial organ development.

Introduction. Knee osteoarthritis is a progressive degenerative disease of the entire joint that leads to functional limitations and reduced quality of life. The end-stage of the disease is associated with disability and a significant burden both for the patient and the society. Osteoarthritis and metabolic syndrome. Metabolic syndrome is a group of cardiovascular risk factors including diabetes and hyperglycemia, abdominal obesity, hypercholesterolemia, and hypertension. The adverse effects of the metabolic syndrome are associated with worsening of the clinical manifestations and disease prognosis through the combined effects of metabolic disorders. It has also been suggested that individual components of the metabolic syndrome may be an independent risk factor for knee osteoarthritis. Osteoarthritis and diabetes mellitus. Experimental and epidemiological evidence supports the role of type II diabetes mellitus in the pathogenesis of osteoarthritis. Chronic hyperglycemia leads to oxidative stress and excessive production of proinflammatory cytokines, while insulin resistance can act locally and systemically through chronic low-grade inflammation. Osteoarthritis and hypertension. The mechanism that explains the relationship between osteoarthritis and hypertension is unclear. Several potential pathways for subchondral bone damage due to hypertension have been described. Osteoarthritis and dyslipidemia. Experimental studies suggest that dyslipidemia may be involved in the pathophysiological process of osteoarthritis, while epidemiological studies show heterogeneous results. Conclusion. Patients with knee osteoarthritis require a holistic approach in which the emphasis is not only on symptomatic pain relief, but also on the treatment of metabolic disorders.

Background / Aim: Metformin is widely used in type 2 diabetes and exhibits many positive biological effects on pancreatic b-cells and muscle cells, such as supporting insulin release by b-cells and glucose uptake by muscle cells and reducing oxidative stress, particularly due to diabetes-associated hyperglycaemia. Interestingly, for type 1 diabetes, transplantation of healthy b-cells has been proposed as a novel way to replace insulin therapy. Recently, bile acid-formulations containing transplantable b-cells showed best stability. Hence, this study aimed to explore the effects of metformin-bile acid formulations in b-cell encapsulation and on the biological activities of b-cells and muscle-cells. Methods: Two sets of biological effects were examined, using metformin-bile acid formulations, on encapsulated b-cells and on muscle cells exposed to the formulations. Results: Various encapsulated b-cell formulations' cell viability, insulin levels, cellular oxidative stress, cellular inflammatory profile and bioenergetics at the normoand hyperglycaemic states showed differing results based upon the metformin concentration and the inclusion or absence of bile acid. Similar effects were observed with muscle cells. Low ratios of metformin and bile acids showed best biological effects, suggesting a formulation dependent result. The formulations' positive effects were more profound at the hyperglycaemic state suggesting efficient cell protective effects. Conclusion: Overall, metformin had positive impacts on the cells in a concentration-dependent manner, with the addition of chenodeoxycholic acid further improving results.

Random geometric hypergraphs are considered as mathematical models of large wireless computer networks. The dependences of the mathematical expectation of the number of hyper-edges in random geometric hypergraphs on the radii of reliable reception / transmission of radio signals by network nodes, as well as on the number of vertices in the hyper- graph are studied. The concepts of the shortest route in a geometric hypergraph are discussed. Calculations of the probabil- ity of connectivity of large random geometric hypergraphs, the mathematical expectation of the diameter of hypergraphs and its change with a change in the radii of the nodes are carried out. The presentation of the results is accompanied by graphs.

Ototoxicity is the damage to inner ear sensory epithelia due to exposure to certain medications and chemicals. This occurs when toxins enter the tightly controlled inner ear environment inducing hair cell death, resulting in hearing loss. Recent studies have explored hydrogel-based bio-nanotechnologies and new drug delivery formulations to prevent drug-induced hearing loss, with much attention given to administration of antioxidant drugs. Bile acids have been recognized as promising excipients due to their biocompatibility and unique physiochemical properties. As yet bile acids have not been explored in improving drug delivery to the inner ear despite improving drug stability and delivery in other systems and demonstrating positive biological effects in their own right.

Armin Mooranian,1,2 Thomas Foster,1,2 Corina M Ionescu,1,2 Louise Carey,1,2 Daniel Walker,1,2 Melissa Jones,1,2 Susbin Raj Wagle,1,2 Bozica Kovacevic,1,2 Jacqueline Chester,1,2 Edan Johnstone,1,2 Jafri Kuthubutheen,3 Daniel Brown,4 Marcus D Atlas,2 Momir Mikov,5 Hani Al-Salami1,2 1The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, Perth, 6102, WA, Australia; 2Hearing Therapeutics, Ear Science Institute Australia, Queen Elizabeth II Medical Centre, Nedlands, Perth, 6009, WA, Australia; 3Fiona Stanley Hospital, Perth, WA, Australia; 4Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia; 5Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, 21101, SerbiaCorrespondence: Hani Al-SalamiHearing Therapeutics, Biotechnology and Pharmaceutical Sciences, Curtin University, Bentley, Perth, 6102, WA, AustraliaTel +61 8 9266 9816Fax + 61 8 9266 2769Email hani.al-salami@curtin.edu.auIntroduction: In a recent study, in our laboratory, primary unconjugated bile acids, commonly found in humans, chenodeoxycholic acid (CDCA), have been shown to improve stability of nanoencapsulated lipophilic drugs and improve their release profile after oral administration likely via electrokinetic stabilisation. Hence, this study aimed to examine the effects of CDCA on exerting similar effects on hydrophilic drugs.Methods: Various CDCA-based formulations were produced for the orally administered hydrophilic drug, metformin. Analyses of these formulations included electrokinetic potentials, topography, drug and CDCA formulation contents, nano size distribution, heat-induced deformation and outer-core expansion indices, release profiles, shell-resistance ratio, and thermal and chemical indices. With the drug’s main target being pancreatic beta-cells, the formulations’ effects on cell viability, functions and inflammatory profiles were also investigated.Results and Conclusions: CDCA-based metformin formulations exhibited improved stability and release profiles via thermal, chemical and electrokinetic effects, which were formulation-dependent suggesting potential applications of CDCA in the oral targeted delivery of hydrophilic drugs.Keywords: microencapsulation, diabetes mellitus, Glyceryl monooleate, Eudragit, chenodeoxycholic acid

Mathematical models of wireless computer networks are considered, reflecting two types of interaction between nodes of the same network — broadcast and routing. A natural form of representation of such a network is a hypergraph, in which the direct links between nodes that do not require routing are specified by the hyper-edges. The routes are chains of hyper-edges. The concepts of geometric and random hypergraphs are introduced, the dependences of the probabilistic characteristics of random geometric hypergraphs on the number of vertices and radii of reliable reception / transmission of radio signals by network nodes are studied — the mathematical expectation and standard deviation of the number of hyperedges, degrees of hyperedges. The properties of dynamic geometric hypergraphs are discussed, their influence on the connectivity of a computer network, and the requirements for algorithms for managing connectivity in terms of hypergraphs are formulated.

The article presents a description of a software package for calculating displacement rates and detecting displacements of the earths surface over areas of intensive coal mining. The complex is built on the basis of the microservice architecture Docker Swarm in integration with the system of massively parallel execution of tasks Apache Spark, as a high-level tool for organizing container-type computations with orchestration of hardware resources. In the software package, the container is used as an element of the sequence of calculation stages of the mathematical model of interferometric processing, presented in the form of a managed service. The service itself is built on the basis of a microkernel of the specified operating system, with support for multitasking of process identifiers and network protocols. Due to the use of containerization of executor objects, the independence of calculations is achieved both within one pool of jobs and between different pools initialized in multi-user mode. The use of the cluster resource manage­ment system and YARN job scheduling made it possible to abstract all the computing resources of the cluster from the specific launch of jobs and to provide dispatching of distributed processing applications. The use in the program code based on the Sentinel-1 Toolbox of the possibility of storing the intermediate results of the operation of procedures in the schemes for calculating the displacement rates makes it possible to carry out calculations with various parameters, and parallelization provides a reduction in the calculation time in comparison with commercial software products. The combination of Docker Swarm and Apache Spark technologies in one software package made it possible to implement the idea of a high-performance computing system based on open source software and cross-platform programming languages Java and Python using low-budget hardware blocks, including those made in Russia.

Deoxycholic acid (DCA) is a bile acid capable of forming micelles and modifying the properties of hydrogels. We incorporated DCA in sodium alginate (SA) and poloxamer 407 matrices creating novel DCA-copolymer hydrogel for therapeutic delivery. Hydrogels were assessed for common rheological properties. Biocompatibility and biological effect were examined on various cell lines. Cell viability was determent in normal and various hypoxic conditions, and full mitochondrial bioenergetic parameters were assessed in cell lines in order to illustrate hydrogel effects on survival, and cell metabolic profile within the hydrogels. Obtained data suggest that a low dose of DCA in permeable, biocompatible hydrogels can be beneficial for cells to combat hypoxic conditions.

Satureja montana L. is traditionally used as spice and for treatment various diseases. Many studies have shown antioxidative effect of Satureja species. Our thorough study in an animal model was performed through measurement of biochemical parameters in the serum, histology analysis and determination of oxidative status of the liver, coupled with investigation of extraction solvent selection using principal component analysis (PCA).Winter savory dry extract (500 mg/kg) dispersion and saline solution were given to Wistar rats for 7 days after exposure to oxidative stress using toxic doses of paracetamol (600 mg/kg). Rats were sacrificed, after which a complete autopsy was performed, the blood obtained was used to determine biochemical parameters, and the liver was sliced for histological analysis and determination of oxidative stress enzymes.Indicators of hepatic and kidney functions, as well as the concentration of oxidative stress enzymes, were statistically significantly lower in animals treated with Satureja montana L. extract compared to the paracetamol group alone before the toxic dose of paracetamol. Liver enzymes were unaltered by pre-treatment with the extract, but the level of lipid peroxidase was decreased, and the level of catalase, glutathione reductase and superoxide dismutase increased proving in vivo antioxidant effect. In addition, the number of inflammatory cells is decreased coupled with activity of CYP2E1 enzymes proving hepatoprotective effect.Satureja montana L. extract in our research has shown hepatoprotective, anti-inflammatory and antioxidative effect. PCA analyses indicated that extraction mediums have a great impact on the antioxidative effect.

We consider mobile computer networks whose stationary movements are forced to change at some points in time by external control actions or random disturbances. External influence can be aimed at the transition of the network to another stationary movement, but during the transition period there is a danger of decreasing the reliability of the network, the quality of its functioning, and even the threat of operability. One of the reasons for this is the rapid change in the topological (graph) characteristics of the network — the loss of connectivity of the dynamic graph of the network, the change in the set of available data transmission routes between nodes. The paper describes the results of statistical modeling of the characteristics of dynamic graphs for perturbed motion, and also presents algorithms for managing dynamic graphs during the transition process, which reduce the negative effects on the network from external influences. Using methods of predictive modeling, the quality of control algorithms is evaluated.

The pulp and paper industry’s multi-tonnage liquid waste is spent cooking liquor containing lignosulfonates, which disposal and processing remains one of the most complex environmental and technological problems, which should be solved. Lignosulfonates have unique colloidal-chemical properties, which determines their high resource potential. However, lignosulfonates’ composition instability often does not provide the properties and indicators set by the consumer. Changing market conditions require constant waste monitoring and modification, that prevents the widespread lignosulfonates use in industrial practice. In this paper, the causes for the formation of lignin-containing waste and its impact on the environment are considered. A strategy for lignosulfonates utilization has been developed, as well as promising methods for these wastes processing and disposal, which will expand the use of lignosulfonates and reduce the pulp and paper industry negative impact on the environment.

Despite a relatively low prevalence of primary brain tumors, they continuously attract scientific interest because of the complexity of their treatment due to their location behind the blood-brain barrier. The main challenge in treatment of brain tumors is not the efficacy of the drugs, per se, but the low efficiency of drug delivery to malignant cells. At the core of the problem is the complex structure of the blood-brain barrier. Nowadays, there is evidence supporting the claim that bile acids have the ability to cross the blood-brain barrier. That ability can be exploited by taking a part in novel drug carrier designs. Bile acids represent a drug carrier system as a part of a mixed micelle composition, bilosomes and conjugates with various drugs. This review discusses the current knowledge related to bile acid molecules as drug penetration modifying agents, with the focus on central nervous system antitumor drug delivery.

The characteristics of random geometric hypergraphs are studied as mathematical models of scalable wireless computer networks. An efficient algorithm for finding cliques in geometric graphs, constructing hypergraphs from geometric configurations has been developed. The types of hyper-edges in hypergraphs generated by a scalable configuration have been identified. The influence of random failures of nodes of computer networks and their restorations on the dynamics of hypergraphs of networks is considered. The analysis of the dynamics of the number of active nodes depending on the type of probability distributions of uptime and recovery time is carried out. The dependences of the mathematical expectation of the number of hyper-edges of certain types in the geometric hypergraph of a wireless computer network on the network operation time, on the radii of zones of reliable reception / transmission of a signal, on the ratio of the parameters of local recovery processes are obtained. The presentation of the results is accompanied by charts.

Antarctica peninsula periphery islands undergo one of the most dramatic ecological changes due to ongoing global warming. The front fields of the Antarctic glaciers are extreme environments and pioneering sites for ecological succession. Rising temperatures lead to deglaciation in the Antarctic habitats, and the new terrain is subjected to the process of soil formation and microbial colonization. In the present study, we investigated the formation of pathogenic fungal soil microbiomes as an effect of forefield deglaciation. Soil samples were taken from two different forefields, one formed several years ago and the other freshly uncovered. Both habitats were in the vicinity of the Perunika Glacier situated in the northeastern direction of Hurd Peninsula, Livingston Island, the second largest island from the South Shetland Archipelago, about 100 km north of the Antarctic Peninsula. Total DNA was extracted and targeted ITS amplicon sequencing was applied. The ITS marker sequences were then taxonomically identified. The abundance of the fungal taxa was calculated. Alpha and Beta diversity analyses to obtain fungal richness in samples were performed. Our results showed that soil habitat formation, initiated by deglaciation, was such that: In the newly deglaciated forefield, there was almost no fungal DNA, which prevented further analysis; At older drier fields metagenome content was much higher; Further analysis showed that the most abundant genera were Pseudogymnoascus, Simplicillium, Hanseniaspora, Mycothermus, and Malassezia. In the newly deglaciated forefield, there was almost no fungal DNA, which prevented further analysis; At older drier fields metagenome content was much higher; Further analysis showed that the most abundant genera were Pseudogymnoascus, Simplicillium, Hanseniaspora, Mycothermus, and Malassezia. It is known that Pseudogymnoascus and Malassezia species have pathogenic keratinolytic activity. In conclusion, the phylum Ascomycota, which dominated the core microbiome showed much higher ecological diversity and abundance, i.e. potential for colonization of the glacier forefields. In contrast, the phylum Basidiomycota appeared to be less fit for these conditions.

Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5®. Genetic polymorphism in CYP3A4, CYP3A5, CYP1A1, CYP2C9, and CYP2C19 was analyzed using PCR-based methods. Multiple linear regression analysis indicated that gender had a significant effect on AUC as the most important pharmacokinetics endpoint, whereas body mass index and age did not show such an influence. Therefore, further analysis considered gender and indicated that both geometric mean values of itraconazole and hydroxy-itraconazole plasma concentrations in men were prominently higher than those in women. A significant reduction of the geometric mean values of Cmax and AUC and increment of Vd in females compared with males were obtained. Analyzed genotypes and gender differences in drug pharmacokinetics could not be related. Non-compartmental and one-compartmental models complemented each other, whereas the application of the two-compartmental model showed a significant correlation with the analysis of one compartment. They indicated a significant influence of gender on itraconazole pharmacokinetics after administration of the single oral dose of the drug, given under fed conditions. Women were less exposed to itraconazole and hydroxy-itraconazole than men due to poorer absorption of itraconazole, its more intense pre-systemic metabolism, and higher distribution of both drug and its metabolite.

Recent preclinical studies in our laboratory have shown that the bile acid profile is altered during diabetes development and such alteration has been linked to the diabetes-associated inflammatory profile. Hence, this study aimed to investigate if the first-line antidiabetic drug metformin will alter the bile acid profile and diabetes-associated inflammation in a murine model of pre-type 2 diabetes. C57 mice were randomly allocated into three equal groups of eight. Group One was given a low-fat diet (LFD), Group Two was given a high-fat diet (HFD), and Group Three was given an HFD and, upon prediabetes confirmation, daily oral metformin for one month. Blood glucose, glycated haemoglobin, drug concentrations in tissues and faeces, and the inflammatory and bile acid profiles were measured. Metformin showed wide tissue distribution and was also present in faeces. The bile acid profile showed significant alteration due to prediabetes, and although metformin did not completely normalize it, it did exert significant effects on both the bile acid and the inflammatory profiles, suggesting a direct and, to some extent, positive impact, particularly on the diabetes-associated inflammatory profile.

Bulgaria, with a high endemicity for malaria in the past, was declared by the WHO as a malaria-free country in 1965. We intended to analyze the epidemiological and clinical implications of imported malaria cases in Bulgaria.This is a retrospective cross-sectional analysis of all recorded cases of imported malaria in Bulgaria over a 21-year period (2000-2020). Patients' clinical records and information gathered from the epidemiological survey of each recorded malaria case were reviewed.A total of 232 cases of imported malaria were reported, 147 (63.4%) were Bulgarian citizens (BC) and 85 (36.6%) were foreign nationals (FN). Two thirds (66.4%) of cases were diagnosed from April to October. Most BCs had travelled for work (66.6%) to Africa (93.9%) and were infected with P. falciparum (83.3%), while most FNs were migrants (54.7%), exposed in Asia (63.5%) with P. vivax infection (62.4%). Clinical complications and a fatal outcome were noted in 14.7% (n = 34) and 3.5% (n = 8) of cases respectively. All complicated cases were in BNs with P. falciparum infection.Bulgaria experiences a steady import of malaria. Efforts to improve diagnosis, management and prevention of malaria, as well as maintenance of a high degree of epidemiological vigilance are needed.

We present a sensor fusion system composed of a micro-electro-mechanical systems (MEMS) inertial measurement unit (IMU) and a stereo camera for land vehicle positioning in global positioning system (GPS)-denied environment. Our approach uses an error state Kalman filter, whose novelty lies in the introduction of two new states: 1) the time synchronization error between visual odometry (VO) and inertial sensors and 2) the VO heading bias. These two error states improve the quality of the vehicle's location estimate, as demonstrated by our tests on real-world data, collected with a sensor-outfitted vehicle. Our approach typically produces a mean circular error of 22 m after 5 min of GPS-denied travel, over an average distance of 1.7 km. These results are in agreement with a best possible theoretical estimate based on the low-cost ADIS16470 IMU, characterized by a 8 °/hr bias instability.

Introduction/Objective. Pain is often an underrecognized entity in children with cerebral palsy. The aim of this study was to determine whether there are differences in pain self-perception between children with cerebral palsy and their caregivers. Methods. This retrospective study included 70 children with cerebral palsy and 70 of their caregivers, treated at the Institute of Child and Youth Health Care of Vojvodina, Serbia. Pain intensity ratings on the Visual Analog Scale (VAS) provided by children and/or their caregivers were analyzed. Results. The research involved 70 children with cerebral palsy and the same number of their caregivers. While only 43 (61.4%) of these children were testable, all 70 caregivers participated. Pain was reported by 19 (44.2%) children and 42 (60%) caregivers, while 17 (39.5%) children suffered from musculoskeletal pain, which was noted by 39 (55.7%) caregivers. Average caregiver rating for musculoskeletal pain for children at Level V, I and III on the Gross Motor Function Classification System (GMFCS) was 6.20 ? 2.10, 2.67 ? 2.18, and 2.50 ? 2, respectively. Average self- and caregiver-reported VAS rating for headache/stomachache was 2.73 ? 1.86 and 2.35 ? 1.49, respectively (p > 0.05). Statistically significant differences were noted in the musculoskeletal pain VAS scores provided by the caregivers for children at different GMFCS levels (p < 0.01). Conclusion. Although no differences in pain perception between children with cerebral palsy and their caregivers have been established, in children with the most severe level of motor disability, caregivers report a statistically higher level of musculoskeletal pain.

Background/Aim: Cardiac arrest (CA) is a leading cause of mortality in the last forty years worldwide. Immediately initiated cardiopulmonary resuscitation (CPR) improves chances for survival. Aim of this study was to determine the efficiency of the Emergency medical service (EMS) dispatch centre in the absence of the uniform emergency medical dispatch assessment protocols in the management of cardiac arrest. Methods: The retrospective and observational study was conducted in Institute for Emergency Medical Service Novi Sad (IEMS Novi Sad) Serbia during a one-year follow-up. The study included patients with out-of-hospital cardiac arrests who underwent CPR. Results: EMS teams of the IEMS Novi Sad had 198 CPRs in the follow-up period. In 142 (71.72 %) calls, the EMS dispatcher got information that the patient was unconscious. The reported reaction time I by the dispatchers for the unconscious patients was 1.37 ± 1.27 minutes, actual duration of the conversation between the dispatcher and a caller - was longer: 138.21 ± 103.02 seconds (p < 0.001). The average conversation time with a caller was 61.37 ± 31.13 seconds. In 6 (4.22 %) cases, the EMS team was dispatched to a patient before the phone call was terminated. At the moment of arrival, all patients were unconscious, 194 (94.37 %) were pulseless, while the remaining 8 (5.63 %) experienced cardiac arrest during the examination. The cardiac arrest was witnessed by a layman in 120 (84.51 %) cases and CPR was initiated by bystanders, before the arrival of the EMS team, only in 13 (10.83 %) patients. Twenty-seven (19.01 %) patients arrived in a hospital with vital signs. Conclusion: The absence of the uniform EMS dispatch assessment protocols for the triage of incoming calls and phone assisted CPR for lay rescuers decreases the survival rate of patients with cardiac arrest.

The microflora of the gastrointestinal tract is essential for mucosal protection, immune education, and for metabolism of humans. Disturbances of these processes results in various diseases. Regarding these processes, there is a clinical interest in the utility of microbial therapy - the feeding of non-pathogenic bacteria, originally derived from the alimentary tract. Considering the commercial success of probiotics, there is still a difficulty for consumers as well as for physicians when choosing the specific product. Since they are classified as food supplements, and not subject to drug regulations, there is ongoing skepticism about the benefits they offer. Fecal bacteriotherapy is reported as highly effective in the treatment of various diseases, including those of the digestive tract. The treatment itself consists of feces infusion from a healthy human donor to the gastrointestinal tract of patient. According to current data, fecal bacteriotherapy represents an emerging and promising low-cost solution for diseases with which antibiotic and probiotic products have been struggling for years.

Introduction. Short bowel syndrome in children is a rare disease. One of the most common etiological factors for the development of short bowel syndrome in children is atresia of the small intestine. After surgical correction of the congenital anomaly, the remaining intestine attempts to increase absorption to restore homeostasis, and the process of intestinal adaptation begins. This process of adaptation can be assisted with analogues of endogenous growth factors of the intestine, such as teduglutide. Case outline. A girl, aged two years and eight months, who had an estimated 20 cm of small intestine after surgical correction of congenital small bowel atresia and clinical signs of short bowel syndrome. She was repeatedly hospitalized due to frequent need for parenteral correction of fluid, electrolyte, and nutrient imbalances. Stagnation in body weight and slow growth in body height were accompanied by weakened gross motor strength and slowed psychophysical development. After exploit conservative treatment measures, stimulation of intestinal adaptation was initiated with the drug teduglutide. After 6 months of drug therapy, progress was observed in body parameters, as well as an increase in intelligence quotient and motor abilities. Conclusion. Short bowel syndrome is a challenging entity for every clinician, and its previous therapy has mainly consisted of parenteral substitution of nutrients, fluids, and electrolytes. Surgical treatment carries the risk of loss of the remaining bowel and lifelong immunosuppression. The pharmacological possibilities of promoting intestinal adaptation using drugs such as teduglutide represent a light at the end of the tunnel for patients with short bowel syndrome.

The paper focuses on telemedicine systems for monitoring the human state and methods of protecting the transmitted data. To assess the state, biosignals are used, which are recorded by sensors and transmitted to a cloud medical information system. Based on the data obtained, a decision is made about the human state. Since the monitoring system works with restricted access information, it must be reliably protected. The study places an emphasis on possible information security threats for all components of the telemedicine system, analyzes various approaches to the protection of transmitted data in remote monitoring systems. It is noted that the existing methods are insufficient and additional methods of protecting the transmitted data are required. It is proposed to assess data security using the information risk management methods

New mathematical models of networks are considered — geometrical oriented graphs. Such models adequately reflect the structure of heterogeneous wireless computer, sensor and other networks. The strongly connected components of geometric digraphs, their dependence on the number of network nodes in a given area, on the distributions of the radii of the zones of reception and transmission of signals are investigated. The probabilistic characteristics of random geometric digraphs, the features of the dependences of the probability of strong connectivity on the number of nodes in the digraphs for various combinations of radii are analyzed.

Despite the growing number of new drugs approved for the treatment of inflammatory bowel disease (IBD), the long-term clinical use of thiopurine therapy and the well-known properties of conventional drugs including azathioprine have made their place in IBD therapy extremely valuable. Despite the fact that thiopurine S-methyltransferase (TPMT) polymorphism has been recognized as a major cause of the interindividual variability in the azathioprine response, recent evidence suggests that there might be some yet unknown causes which complicate dosing strategies causing either failure of therapy or toxicity. Increasing evidence suggests that gut microbiota, with its ability to release microbial enzymes, affects the pharmacokinetics of numerous drugs and subsequently drastically alters clinical effectiveness. Azathioprine, as an orally administered drug which has a complex metabolic pathway, is the prime illustrative candidate for such microbial metabolism of drugs. Comprehensive databases on microbial drug-metabolizing enzymes have not yet been generated. This study provides insights into the current evidence on microbiota-mediated metabolism of azathioprine and systematically accumulates findings of bacteria that possess enzymes required for the azathioprine biotransformation. Additionally, it proposes concepts for the identification of gut bacteria species responsible for the metabolism of azathioprine that could aid in the prediction of dose-response effects, complementing pharmacogenetic approaches already applied in the optimization of thiopurine therapy of IBD. It would be of great importance to elucidate to what extent microbiota-mediated metabolism of azathioprine contributes to the drug outcomes in IBD patients which could facilitate the clinical implementation of novel tools for personalized thiopurine treatment of IBD.