Sofia University "St. Kliment Ohridski"

Substance use disorder (SUD) is a complex condition involving psychological, sociocultural, and genetic factors. In this study, we examined the alternations in mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) and their relationship to demographic, medical, heredity, and substance use characteristics in patients with SUD and healthy controls. We investigated a total cohort of 54 participants: 21 healthy individuals, 17 patients with alcohol dependence (AD), and 16 patients with drug dependence (DD). TL and mtDNAcn were measured using quantitative real-time PCR, with statistical methods used to assess the association between variables. We observed a significant decrease in mtDNAcn in both SUD groups, particularly associated with chronic diseases in the AD group. No significant differences in TL were found among the three groups. Sex-associated analysis revealed a significant mtDNAcn reduction in the DD males and elevated TL in AD males compared to control males. Correlation analyses showed associations between the two biomarkers and age, sex, and chronic diseases. Our findings suggest that leukocyte mtDNAcn is a more sensitive marker than TL in patients with SUD, indicating sex-specific patterns of alterations. These findings require confirmation through larger cohort recruitment.

Myopia is a type of clinical refraction, a form of spherical refractive anomaly in which the eye has a relatively stronger refractive power for the corresponding length of the anteroposterior axis. The focus of this optical system is far in front of the retina. Myopia can be congenital or manifest later, most often at school age. It can be stationary or progressive. Progresive myopia is sight-threatening. The article discusses results from a screening program for myopia progression in Bulgarian schools between 2018-2023. The risk factors for myopia development have been outlined, and the ways of prophylaxis have been pointed out.

Citation: Penchev, H.; Dimitrov, E.; Novakov, C.; Haladjova, E.; Veleva, R.; Moskova-Doumanova, V.; Topouzova-Hristova, T.; Rangelov, S. Abstract: Ladder oligomers containing calixarene skeletons in the main chain-calix[4]resorcinarene (CRA) ladder macromolecules with open chain and cyclic macromolecules with double ring-like (Noria-type) topologies-bring particular research attention as functional materials with various applications. However, there is still a remarkable lack of studies into the synthesis of fully water-soluble derivatives of these interesting macromolecules. Research on this topic would allow their bio-based research and application niche to be at least revealed. In the present study, a strategy for the synthesis of water-soluble polyglycidol-derivatized calix resorcinarene ladder oligomers with open chain and cyclic structures is introduced. A grafting from approach was used to build branched or linear polyglycidol chains from the ladder scaffolds. The novel structures were synthesized in quantitative yields and fully characterized by NMR, FTIR and UV-vis spectroscopy, gel permeation chromatography, MALDI-TOF mass spectrometry, analytical ultracentrifugation, and static light scattering to obtain the molar mass characteristics and composition. The biocompatibility and toxicity of the two polyglycidol-derivatized oligomers were investigated and the concentration dependence of the survival of three cell lines of human origin determined. The selective apoptosis effect at relatively low dissolve concentrations toward two kinds of cancerous cell lines was found.

For the first time, N-modified analogues of VV-hemorphin-5 (Valorphin) were synthesised and conjugated with three different 4-substitured-1,8-naphthalimides (H-NVal without substituent, Cl-NVal with chloro-substituent, and NO2-NVal with nitro-substituent). Cotton fabric was modified with these peptides by soaking it in their ethanol solution, and the colourimetric properties of the obtained fabric were measured. The fluorescent analysis shows that peptide immobilisation on a solid matrix as fabric decreases the molecule flexibility and spectrum maxima shift bathocromically with the appearance of a vibrational structure. The peptides’ contact antimicrobial activity, and the resulting fabrics, have been investigated against model Gram-positive B. cereus and Gram-negative P. aeruginos bacteria. For the first time, the influence of light on bacterial inactivation was investigated by antibacterial photodynamic therapy of similar peptides. Slightly more pronounced activity in liquid media and after deposition on the cotton fabric was obtained for the peptide containing 4-nitro-1,8-naphthalimide compared to the other two peptides. Immobilisation of a peptide on the surface of fibres reduces their antimicrobial activity since their mobility is essential for good contact with bacteria. Cotton fabrics can be used in medical practice to produce antibacterial dressings and materials.

The angiotensin-converting enzyme-2 (ACE2) is a transmembrane glycoprotein, consisting of two segments: a large carboxypeptidase catalytic domain and a small transmembrane collectrin-like segment. This protein plays an essential role in blood pressure regulation, transforming the peptides angiotensin-I and angiotensin-II (vasoconstrictors) into angiotensin-1-9 and angiotensin-1-7 (vasodilators). During the COVID-19 pandemic, ACE2 became best known as the receptor of the S-protein of SARS-CoV-2 coronavirus. The purpose of the following research is to reconstruct the 3D structure of the catalytic domain of the rabbit enzyme rACE2 using its primary amino acid sequence, and then to compare it with the human analog hACE2. For this purpose, we have calculated the electric properties and thermodynamic stability of the two protein globules employing computer programs for protein electrostatics. The analysis of the amino acid content and sequence demonstrates an 85% identity between the two polypeptide chains. The 3D alignment of the catalytic domains of the two enzymes shows coincidence of the α-helix segments, and a small difference in two unstructured segments of the chain. The electric charge of the catalytic domain of rACE2, determined by 70 positively chargeable amino acid residues, 114 negatively chargeable ones, and two positive charges of the Zn2+ atom in the active center exceeds that of hACE2 by one positively and four negatively chargeable groups; however, in 3D conformation, their isoelectric points pI 5.21 coincide. The surface electrostatic potential is similarly distributed on the surface of the two catalytic globules, but it strongly depends on the pH of the extracellular medium: it is almost positive at pH 5.0 but strongly negative at pH 7.4. The pH dependence of the electrostatic component of the free energy discloses that the 3D structure of the two enzymes is maximally stable at pH 6.5. The high similarity in the 3D structure, as well as in the electrostatic and thermodynamic properties, suggests that rabbit can be successfully used as an animal model to study blood pressure regulation and coronavirus infection, and the results can be extrapolated to humans.

In this paper, we investigate a Lyapunov trajectory tracking design method that incorporates a Schrödinger equation with a dipole subterm and polarizability. Our findings suggest that the proposed control law can overcome the limitations of certain existing control laws that do not converge. By integrating a quadratic performance index, we introduce an optimal control law, which we subsequently analyze for stability and optimality. We also simulate the spin-1/2 particle system to illustrate our results. These findings are further validated through numerical illustrations involving a 3D, 5D system, and a spin-1/2 particle system.

It is well known that perception and cognition are systematically biased towards the recent past. That is, a decision about the current state of a perceptual feature (e.g. orientation) can be predicted based on a recent state of the same feature. Such serial dependencies have been demonstrated across perception, memory and cognition, and have been jointly attributed to an adaptive mechanism meant to promote stability in a constantly changing environment. Here, we argue that this adaptive mechanism prioritizes past information on the most basic structural level, such that the strength of the attractive bias is modulated by the amount of structural coherence in stimuli. We presented visual patterns of varied structural disorder (randomness) prior to a recognition memory decision that required discriminating between trained and novel visual patterns. Both highly generic geometrical shapes and completely random patterns failed to elicit an effect on decisional response times. By contrast, we found recognition memory decisions to be significantly faster in trials where the irrelevant probe pattern was ‘optimally’ random. This result suggests that decision-making is influenced by the past’s informational worth. More importantly, it suggests an optimal amount of uncertainty to facilitate future decisions.

The aim of the study is to analyze reports of adverse drug reactions published in the scientific literature occurring during and after the use of kinase inhibitors for the treatment of rheumatologic diseases to determine their type, frequency, and severity. The search was conducted in the MEDLINE and PubMed databases from January 2005 to May 2022. We found a total of 291 publications, from which we selected suitable ones for data extraction. We conducted descriptive and variation analyses as the main statistical analyses. We determined mean values, standard deviation, minimum, maximum, and 95% confidence intervals. The PICOS tool was used to evaluate the results. The analyzed population includes patients with rheumatologic and oncologic diseases. There is a significant interest in the drug safety of kinase inhibitors, as they represent a rapidly evolving and reliable pharmacological class. Clarifying the safety profile of their representatives remains important. In-depth review of full-text publications shows that the high frequency of reported serious ADRs is rather due to increased interest in reporting and publishing these cases than to their high frequency of occurrence.

Silica–poly (vinylpyrrolidone) hybrid material was prepared using the sol–gel method. Tetramethyl ortosilane (TMOS) was used as a silica precursor. XRD analysis established that the as-prepared material is amorphous. The morphological structure of the final product was determined by the incorporated PVP. The UV–Vis analysis showed that the obtained hybrid exhibited absorption in the ultraviolet range. The antimicrobial activity of the SiO2/15PVP hybrid material was tested on Staphylococcus epidermidis ATCC 14990, Salmonella typhimurium ATCC BAA-2162, Candida albicans, and Saccharomyces cerevisiae in combination with the following antibiotics: Vancomycin for Gram-positive bacteria, Ciprofloxacin for Gram-negative bacteria, and Nystatin for yeast. The results confirmed a concentration-dependent synergistic effect of the antibiotic in combination with the TM15/PVP hybrid particles, especially at their highest concentration of 100 mg/mL on Gram-positive bacteria and for the Gram-negative Salmonella. On Candida albicans ATCC 18804 and Saccharomyces cerevisiae CCY 21-6-3, the effect was synergistic again, and a fungicidal effect was observed at 6.25 and 1.50 mg/mL for the antibiotic concentration and concentrations of hybrid material at 100 mg/mL. The toxicity on Daphnia magna was also tested. The registered prooxidant activity of SiO2/15PVP shows possible applications at very low concentrations. The obtained results demonstrate the possibility of clinical implementations of the newly synthesized hybrid material.

Monensic acid is a natural polyether ionophore and is a therapeutic of first choice in veterinary medicine for the control of coccidiosis. Although known as a sodium-binding ligand, it can also form a variety of coordination species depending on experimental conditions applied. In this study, we present the crystal structures and properties of Co(II) and Mn(II) complexes of sodium monensinate (MonNa) derived from the reaction of MonNa with cobalt or manganese dinitrates. The newly obtained coordination compounds have the same composition [M(MonNa)2(NO3)2] but the transition metal ions are placed in a different environment. The two nitrate ligands behave mono- or bidentately bound in the Co(II)- and Mn(II)-containing species, respectively, while the monensinate ligands act in a similar manner through their monodentate carboxylate functions. The formed CoO4 and MnO6 units determine the geometry of the corresponding inner coordination cores of the complexes as a tetrahedron in the case of Co(II), and as a strongly distorted octahedral structure in Mn(II) species. The effect of inorganic anions on the antibacterial performance of sodium monensinate appears to be negligible, while the presence of Co(II) or Mn(II) cations preserves or enhances the activity of unmodified MonNa, which differentially affects the growth of Bacillus subtilis, Bacillus cereus, Kocuria rhizophila, Staphilococcus aureus, and Staphilococcus saprophyticus strains.

Many endocrinopathies demonstrate dermatological manifestations that facilitate previously undiagnosed endocrine disorders with maternal and fetal ramifications. Maternal and fetal risks depend significantly on early diagnosis and management of these endocrinopathies in order to prevent perinatal mortality and increased overall morbidity. A plethora of systemic and dermatological inflammatory conditions may develop in the course of pregnancy complicated with diabetes. Maternal obesity and gestational insulin resistance also provoke low-grade inflammation, which downregulates placental leptin gene expression and diminishes tumor necrosis factor alpha and interleukin-6 in the fetus, causing placental morphometry changes and higher fetus weight. Markers of microangiopathy such as impaired endothelial permeability and increased intima thickness are detected in higher levels in pregnant diabetic patients. Hence, pregnancy acts as a “stress test” to identify women with diabetic predisposition and susceptibility to chronic persistent inflammation. Dermatological disorders that evolve during pregnancy are classified in two main categories: specific conditions that occur more commonly or exacerbate during pregnancy and diabetes-related skin diseases. Their prompt verification insured by a highly qualified multidisciplinary team of an obstetrician, a dermatologist, and an expert endocrinologist helps to optimize management and improve outcomes. Diabetes prevention requires lifestyle changes and exercise promotion to prevent a healthier mother and child’s future. Insulin is the first choice of treatment in complicated cases. The role of other antihyperglycemic agents requires more sophisticated and larger randomized controlled studies to evaluate their efficacy and safety.

We consider the extremal problem of interpolation of convex scattered data in ℝ3${\mathrm{\mathbb{R}}}^3$ by smooth edge convex curve networks with minimal Lp${L}_p$‐norm of the second derivative for 1<p≤∞$1<p\le \infty$. The problem for p=2 p=2 was set and solved by Andersson et al. (1995). Vlachkova (2019) extended the results of Andersson et al. (1995) and solved the problem for 1<p<∞$1<p<\infty$. The minimum edge convex Lp${L}_p$‐norm network for 1<p<∞$1<p<\infty$ is obtained from the solution to a system of nonlinear equations with coefficients determined by the data. The solution in the case 1<p<∞$1<p<\infty$ is unique for strictly convex data. The corresponding extremal problem for p=∞$p=\infty$ remained open. The case p=∞$p=\infty$ is of particular interest in the context of applications since it has a solution which is a smooth curve network consisting of quadratic splines, that is, a smooth curve network of the lowest possible computational complexity. Here, we show that the extremal interpolation problem for p=∞$p=\infty$ always has a solution. We give a characterization of this solution. We show that a solution to the problem for p=∞$p=\infty$ can be found by solving a system of nonlinear equations in the case where it exists.

In this work, we consider moments of exponential functionals of Lévy processes on a deter-ministic horizon. We derive two convolutional identities regarding these moments. The first one relates the complex moments of the exponential functional of a general Lévy process up to a deterministic time to those of the dual Lévy process. The second convolutional identity links the complex moments of the exponential functional of a Lévy process, which is not a compound Poisson process, to those of the exponential functionals of its ascending/descending ladder heights on a random horizon determined by the respective local times. As a consequence, we derive a universal expression for the half-negative moment of the exponential functional of any symmetric Lévy process, which resembles in its universality the passage time of symmetric random walks. The (n − 1/2) th , n ≥ 0 moments are also discussed. On the other hand, under extremely mild conditions, we obtain a series expansion for the complex moments (including those with negative real part) of the exponential functionals of subordinators. This significantly extends previous results and offers neat expressions for the negative real moments. In a special case, it turns out that the Riemann zeta function is the minus first moment of the exponential functional of the Gamma subordinator indexed in time.

This article investigates how two Communist forced labour camps, Belene in Bulgaria and Goli Otok in Croatia, became sites of memory and remain icons of political repression and state-organized torture. The article discusses how the public memory of the two camps has been shaped through vivid depictions in former inmates’ memoirs and in works of fiction. It analyzes recent debates about the preservation and institutionalization of these sites of memory and about what, whom, and how to commemorate. As a further step, it investigates how the camp sites have attracted visitors interested in so-called dark tourism. The article explores the creation of a literary tradition of memory by tracing the writings that have helped to establish Belene and Goli Otok as sites of memory of political repression in Bulgaria and Croatia, and it examines the processes involved in the construction of the physical sites as heritage sites and tourist attractions.

This paper explores the transitory imaginaries in the semi-permanent constitutional polytransition in the Central and Eastern European region. It is centered on the novel concept of transitory imaginaries. This concept serves as a tool for combined socio-legal, comparative, and semiotic approach to constitutional transitions. The paper demonstrates the deep conceptual and pragmatic links between constitutional transitology, memory politics, and identity politics. It exposes the role of the forms of symbolic-imaginary constitutionalism for shaping and understanding of constitutional transitions and polytransitions. The paper shows the importance of constitutional imagination for collective symbolic-imaginary sublimation of constitutional transition and the bridging role of constitutional imaginaries that are stretched between the constitutional past, the constitutional present, and the constitutional future. In that regard, the paper explores the different ways for imagining the constitutional past and constitutional future and offers an outline of the main imaginaries in serving that purpose. More precisely, the paper analyses nationalist transitory imaginaries, universalist transitory imaginaries, and prospective transitional imaginaries.

Background: Zinc oxide nanoparticles are safe, non-toxic, and biocompatible. These NPs are used in food packaging materials, self-cleaning glass, ceramics, deodorants, sunscreens, paints, coatings, ointments, lotions, and as preservatives. This study explored the biological potential of ZnO nanoparticles synthesized using H. rariflorum. Methods: In vitro antibacterial and antifungal ac-tivities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Sal-monella typhi, Candida albicans, Penicillium notatum, Aspergillus flavus, Aspergillus niger and Aspergillus solani were determined. Antioxidant activity was explored using the DPPH radical scavenging method. In vivo analgesic, antipyretic and sedative potential of synthesized nanoparticles was investigated using a mouse model. Results: SEM with various magnification powers showed that some particles were spherical while some were aggregated, flake-shaped, and hexagonal with rough and irregular surfaces. The EDX analysis revealed Zn (12.63%), O (22.83%) and C (63.11%) with trace quantities of Si (0.40%), Ca (0.54%) and P (0.49%). The XRD pattern indicated an amorphous state, with no peaks observed throughout the spectrum. The UV–visible spectro-photometry revealed a characteristic absorption peak at 375 nm, indicating the presence of ZnO nanoparticles. Fourier Transform Infrared Spectroscopy (FTIR) displayed several small peaks between 1793 and 2370 cm−1, providing evidence of the presence of different kinds of organic compounds with different functional groups. ZnO-NPs showed dose-dependent antibacterial and antifungal potential against all strains. Staphylococcus aureus and Candida albicans were the most susceptible strains. The nanoparticles exhibited a maximum antioxidant effect of 85.28% at 100 μg/mL. In this study, the acute toxicity test showed no mortality, and normal behavior was ob-served in mice at ZnO-NP doses of 5, 10, and 20 mg/kg. For analgesic and antipyretic activities, a two-way ANOVA revealed that dose, time, and the interaction between dose and time were sig-nificant. In contrast, the samples had a non-significant effect on sedative activity. Conclusions: This innovative study suggests a potential use of plant resources for managing microbes and treating various diseases, providing a scientific basis for the traditional use of H. rariflorum.

Convection monitoring and forecasting are crucial for air traffic management as they can lead to the development of intense thunderstorms and hazards such as severe turbulence and icing, lightning activity, microbursts and hail that affect aviation safety. The airport of Burgas is located in southeast Bulgaria on the Black Sea coast and occurrences of intense thunderstorms are mainly observed in the warm season between May and September. This work presents an analysis of severe convection over southeast Bulgaria on 17 September 2022. In the late afternoon, a gust front was formed that reached the Burgas airport with a wind speed exceeding 45 m/s, the record for the past 50 years, damaging the instrument landing system of the airport. To analyse the severe weather conditions, we combine state-of-the-art observations from satellite and radar with the upper-air sounding and surface. The studied period was dominated by the presence of a very unstable air mass over southeast Bulgaria ahead of the atmospheric front. As convection developed and moved east towards Burgas, it had four characteristics of severe deep convection, including gravitational waves at the overshooting cloud top, a cold U-shape, a flanking line and a cloud top temperature below −70 °C. The positive integrated water vapour (IWV) rate of change preceded the lightning activity peak by 30 min. Analysis of integrated vapour transport (IVT) gives higher values by a factor of two compared to climatology associated with the atmospheric river covering the eastern Mediterranean sea.