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Abstract In calcium imaging studies, Ca2+ transients are commonly interpreted as neuronal action potentials (APs). However, our findings demonstrate that robust optical Ca2+ transients primarily stem from complex “AP-Plateaus”, while simple APs lacking underlying depolarization envelopes produce much weaker photonic signatures. Under challenging in vivo conditions, these “AP-Plateaus” are likely to surpass noise levels, thus dominating the Ca2+ recordings. In spontaneously active neuronal culture, optical Ca2+ transients (OGB1-AM, GCaMP6f) exhibited approximately tenfold greater amplitude and twofold longer half-width compared to optical voltage transients (ArcLightD). The amplitude of the ArcLightD signal exhibited a strong correlation with the duration of the underlying membrane depolarization, and a weaker correlation with the presence of a fast sodium AP. Specifically, ArcLightD exhibited robust responsiveness to the slow “foot” but not the fast “trunk” of the neuronal AP. Particularly potent stimulators of optical signals in both Ca2+ and voltage imaging modalities were APs combined with plateau potentials (AP-Plateaus), resembling dendritic Ca2+ spikes or “UP states” in pyramidal neurons. Interestingly, even the spikeless plateaus (amplitude > 10 mV, duration > 200 ms) could generate conspicuous Ca2+ optical signals in neurons. Therefore, in certain circumstances, Ca2+ transients should not be interpreted solely as indicators of neuronal AP firing.

Aim. To study the association of comorbidities and treatment outcomes in tuberculosis (TB) patients. Materials and methods. A retrospective study includes all TB patients aged 18 years and older registered for treatment in Moscow in period 2021 the end of the 3rd quarter of 2022 using data of regional epidemiological TB monitoring system, a total of 3039 patients. The frequency and spectrum of comorbidities, its impact on the risk of adverse treatment outcome (ATO) and mortality using univariate and regression analysis were assessed. Results. Comorbidities were identified in 1528 (50.3%) patients (95% confidence interval – CI 48.5–52.1); HIV infection (18.0%), chronic nonspecific lung disease (9.6%) and cardiovascular disease (8.2%) were predominant. The presence of comorbid pathology increased the odds of uneffective treatment (odds ratio – OR 2.56, 95% CI 2.22–3.03) and death (OR 2.45, 95% СI 1.67–3.59). Independent risk factors for ATO were HIV infection (OR 4.10, 95% CI 3.36–5.10), substance use (OR 2.57, 95% CI 1.70–3.66), chronic nonspecific lung disease (OR 1.39, 95% CI 1.04–1.88), diabetes mellitus (OR 1.69, 95% CI 1.15–2.48), liver pathology (OR 2.10, 95% CI 1.46–3.03), mental illness (OR 2.01, 95% CI 1.32–3.06). The death rate was 13.4%; the most significant predictors of mortality were HIV infection (OR 3.89, 95% CI 2.42–6.22) and liver disease (OR 1.90, 95% CI 1.27–2.82). A comorbidome model was constructed to assess the importance of different comorbidities for patient prognosis. Conclusion. The presence of comorbidity (predominantly HIV infection and liver disease) is a significant risk factor for ATO and mortality in TB patients, which should be taken into account when organizing and providing TB care to comorbid patients.

Abstract Background Systemic sclerosis (SSc) is considered by many to be one of the most severe autoimmune rheumatic diseases with lower prevalence observed in Northern Europe. No previous studies on the prevalence of SSc in Latvia have been conducted and the aim was to study the demographic and clinical data of patients with SSc in northeastern Europe country. Methods This study was conducted in two main Latvian hospitals for adults and includes patients with SSc who were consulted between 2016 and 2021. Results During the study period, 159 patients with SSc were consulted. The point prevalence on 1 January 2021 was 84.0 per million. Female to male ratio was 4.67:1, and highest gender ratio was observed in the age group 70–79-year (6.75:1). Antinuclear antibodies were present in 82.58% of patients, without gender difference. Centromere pattern was more frequently observed in females (40.19% vs. 19.04%), in contrast to speckled pattern (50.98% vs. 57.14%). At disease onset females tended to be younger (46.51 ± 13.52) than males (50.5 ± 16.64). Males had more diffuse cutaneous subtype, interstitial lung disease, pulmonary hypertension and esophageal dysmotility. More than half of patients received treatment with glucocorticoids at any point of the disease (68.31%), without gender difference. Conclusions Systemic sclerosis is less common in Latvia than in other countries and regions. Due to its location, the data from Latvia are consistent with a north-south gradient in Europe. Gender ratio differences persisted in older age groups as well. Antinuclear antibodies presence did not differ between genders, but in female’s centromere pattern was much more likely to be present. Males had more severe disease course, but in both genders more than half of patients received treatment with GCs at any point of the disease.

Abstract Tiger sharks are apex predators with a circumglobal tropical and warm-temperate distribution, with a general lack of population data for the central Indian Ocean. In Fuvahmulah, Maldives, tiger sharks display frequent use of the harbour area, attracted by discarded fish waste. Here, we document the population structure, residency, and reproductive characteristics of the world’s largest known tiger shark aggregation in a geographically-restricted area. Using non-invasive methods, photo identification and laser photogrammetry, we identified 239 individual tiger sharks over a 7-year study period. The aggregation was female-dominated (84.5%), with both large juveniles and adults present. Adult females were resighted over the entire study period displaying strong inter- and intra-annual site fidelity. Modelled residency using maximum likelihood methods suggests they spent 60.7 ± S.E. 7.5 days in Fuvahmulah, with a larger aggregation size, shorter residence periods and longer absence periods compared to juvenile females. Prolonged abdominal distensions of adult females indicate they likely stay near Fuvahmulah during gestation and reproduce biennially. Fuvahmulah seems to provide suitable conditions for gestation given the year-round provision of food and warm waters, exhibited by strong site fidelity and temporal residency. Our results show indications of a thriving population within the confines of protected waters.

Background: Ovarian tumors are characterized by asymptomatic progression until their late stages, when at the time of diagnosis the patient already has extensive metastatic disease. In addition to lymphogenous and hematogenous metastasis in ovarian cancer, there are peritoneal dissemination and metastasis to the greater omentum with ascites; moreover, peritoneal carcinomatosis is the predominant route of metastasizing of ovarian cancer. Epigenetic factors, such as gene methylation, regulatory microRNAs and long non-coding RNAs (lncRNAs), contribute to progression of this cancer. Our previous bioinformatic and experimental studies have identified 13 genes of lncRNAs (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) hypermethylated in the ovarian neoplasms. Aim: To evaluate the clinical significance of methylation levels of 13 lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) associated with various types of ovarian cancer metastasis, including lymphogenous, peritoneal, omental, and distant metastases. Methods: The methylation levels of lncRNA genes GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1 were analyzed by quantitative real-time methylation-specific polymerase chain reaction. We tested 122 duplicate samples of ovarian neoplasms, including 104 malignancies and 18 borderline tumors, as well as 45 peritoneal macro metastases, collected in the N.N. Blokhin National Medical Research Center of Oncology in 2020 to 2023. The study included 21 samples of primary tumor from patients with lymphogenous metastases, 45 samples from patients with peritoneal dissemination, 61 from those with omental metastases, 49 from patients with ascites, and 9 with distant metastases. Results: The tumor samples from the patients with lymphatic nodes metastases showed a significant increase in the methylation level of two lncRNA genes: SNHG6 (p = 0.044) and SNHG12 (p = 0.006). Peritoneal dissemination was associated with hypermethylation of four lncRNA genes: GAS5, HOTAIR, LINC00472 (p 0.05), and most significantly TINCR (p = 0.001). GAS5, HOTAIR, LINC00886 (p 0.05) and most significantly LINC00472 (p 0.001) hypermethylation was typical for omental metastasis, and that of LINC00472 and LINC00886, with ascites (p 0.05). Peritoneal macroscopic metastases demonstrated increased methylation of MAFG-DT (p 0.001) and TP53TG1 (p 0.001) and desmethylation of LINC00886 (p = 0.003) and SNHG12 (p = 0.002), compared to their primary tumors. Conclusion: We performed the analysis of clinical significance of 13 hypermethylated lncRNA genes in ovarian cancer and were the first to show that 10 genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, SNHG6, SNHG12, TINCR, TP53TG1, TUG1) were associated with various types of ovarian tumor metastasis. Also, we were able to determine certain panels of lncRNA, which, if demonstrate abnormal methylation, were specific for lymphogenous and peritoneal metastasis of ovarian tumors.

Abstract Carbon Capture, Utilization, and Storage (CCUS) offers a viable solution to reduce the carbon footprint in the petroleum industry, and foam injection presents a promising method to achieve this while simultaneously increasing oil recovery. In this work, we studied the feasibility of CO2 foam for co-optimizing enhanced oil recovery and CO2 storage in a high-salinity carbonate formation. The simulated hydrodynamic model is a depleted formation containing 30% residual oil, with three mechanisms for CO2 storage: solubility, residual, and mineralization trapping mechanisms. The results showed that after 20 years, oil recovery during foam injection was 2.7 times higher than CO2 injection, and the CO2 stored during foam flooding was 38% higher than CO2 injection. Notably, foam injection also increased CO2 storage capacity by 2.6 times, indicating the potential to store around 2 gigatons of CO2 in the simulated model. This was attributed to the ability of foam to significantly reduce gas mobility and thus form isolated bubbles through its Jamin effect. Residual trapping was the dominant trapping mechanism, contributing to over 70% of the total CO2 trapped, attributed to the reduction in the dissolution of CO2 in brine due to the high salinity of the aqueous medium. CO2 mineralization was also studied, showing the least trapping efficiency and the dissolution trend of all the carbonate minerals. This study illustrates a novel CO2 utilization and storage technique in which CO2 is concurrently sequestered while enhancing oil recovery in a depleted oil reservoir by injecting CO2 as foam. The relevance of this study lies in its potential to provide a dual benefit of reducing greenhouse gas emissions and boosting oil production, offering a sustainable approach for the petroleum industry.

Objective: validation of the Russian-language version of Ankylosing Spondylitis Quality of Life (ASQoL) specific questionnaire for patients with ankylosing spondylitis (AS). Materials and methods. Тhe study included 100 patients with a definite diagnosis of AS according to the modified New York criteria of 1984. Patients were mostly men (58.5%), average age – 38.6±10 years, disease duration – 10.3±7.0 years, median disease activity by ASDAS-CRP – 2.32 [1.45; 2.94]. At the initial visit and after 3 months, all patients underwent a standard rheumatological examination, with assessment of the tender joint count (TJC) and swollen joint count (SJC) out of 44 joints assessed, the number of inflamed entheses using MASES index, spinal mobility using BASMI index. Assessment of patient reported outcomes included an assessment of spinal pain, night spinal pain, spinal pain during the day using a numerical rating scale, patient’s global assessment of health, assessment of functional status using BASFI index and health related quality of life (HRQoL) using EQ-5D, SF-36 and ASQoL questionnaires. To determine reliability of ASQoL questionnaire, a test-retest analysis and determination of internal consistency by calculating the Cronbach's α coefficient were used. The reliability of the questionnaire was analyzed in 39 patients. To assess the validity of the ASQoL questionnaire, i.e. its ability to reliably measure its inherent characteristics, construct and criterion validity were determined. The sensitivity of the questionnaire was assessed after 3 months during therapy in 79 patients. Results and discussion. According to the test-retest analysis, there was no difference between the initial assessment and re-assessment after 3 days (p>0.05), the Cronbach α coefficient was 0.884, indicating high reliability. Construct validity analysis was carried out using factor analysis and the “known groups” method. 3 main factors were identified: pain, physical health, emotional health. The “known groups” method showed that in patients with high disease activity according to ASDAS-CRP and BASDAI, HRQoL was significantly worse than in patients with low disease activity (р

Introduction: The disorder known as burnout develops as a reaction to the damaging impacts of workplace stress. When occupational stress is poorly managed, it can result in burnout, which has a detrimental impact on workers’ performance and emotional and physical well-being. Those who work in the helping profession are the most vulnerable. Pharmacy practitioners are among the most vulnerable groups in the healthcare industry. Aim: The aim of the study was to look into how community pharmacists’ work environments affect their levels of occupational burnout. Materials and methods: The current survey included 127 pharmacists holders of a Master of Pharmacy degree who practice in Bulgaria’s northeast. A paper-based questionnaire with details about the workplace of these pharmacists and the Maslach Burnout Inventory (MBI-HSS-MP), a validated assessment instrument, were used to conduct the survey. Results: The majority of those surveyed (53%) had a medium to high degree of burnout at work. The highest percentage of pharmacists (51%) received high scores on the depersonalization scale, which is associated with a lack of motivation for providing patient care. The degree of burnout was found to be unaffected by the kind of community pharmacy – chain or individually owned. Burnout was more prevalent among responsible and non-responsible pharmacists than among pharmacy owners. Conclusion: It was determined that pharmacists needed training and preventative measures to avoid occupational burnout, even though there was no evidence of a statistically significant relationship between the job position and burnout.

Aim: The aim of this randomized clinical trial was to compare the qualitative (linear alveolar ridge changes) and quantitative (healing complications) outcomes after guided bone regeneration (GBR) using a custom-made 3D printed titanium mesh versus titanium reinforced dense PTFE membrane for vertical and horizontal augmentation of deficient alveolar ridges. Materials and methods: Forty patients (40 defect sites) were included in the analysis. The patients were divided into two groups – a test group that received custom made Ti mesh and a control group which received a titanium reinforced dense polytetrafluoroethylene membrane. This case series documented consecutive patients treated with vertical bone augmentation to facilitate the future placement of dental implants. The procedure was performed using xenograft and autograft in a ratio of 1:1. Baseline vertical and horizontal deficiencies, acquired bone height and width as well as absolute bone gain (height and width) were recorded radiographically; postoperative complication rate was recorded clinically. Results: The absolute bone height acquired for the test group was 3.65±1.73 mm, and for the control group - 4.24±2.19 mm; the absolute bone width acquired for the test group was 2.48±1.03 mm and for the control group - 2.60±0.82 mm. Postop complication rate was 33.3% for the test group and 38.9% for the control group. Conclusion: The use of a custom-made 3D printed titanium mesh for needs of vertical and horizontal guided bone regeneration showed results comparable to those of – Ti d-PTFE both in terms of height and width gain and complication rate.

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pneumonia with extremely heterogeneous clinical presentation, ranging from asymptomatic to severely ill patients. Previous studies have reported links between the presence of host genetic variants and the outcome of the COVID-19 infection. In our study, we used whole exome sequencing in a cohort of 444 SARS-CoV-2 patients, admitted to hospital in the period October-2020–April-2022, to search for associations between rare pathogenic/potentially pathogenic variants and COVID-19 progression. We used gene prioritization-based analysis in genes that have been reported by host genetic studies. Although we did not identify correlation between the presence of rare pathogenic variants and COVID-19 outcome, in critically ill patients we detected known mutations in a number of genes associated with severe disease related to cardiovascular disease, primary ciliary dyskinesia, cystic fibrosis, DNA damage repair response, coagulation, primary immune disorder, hemoglobin subunit β, and others. Additionally, we report 93 novel pathogenic variants found in severely infected patients who required intubation or died. A network analysis showed main component, consisting of 13 highly interconnected genes related to epithelial cilium. In conclusion, we have detected rare pathogenic host variants that may have influenced the COVID-19 outcome in Bulgarian patients.

Abstract Counterstereotypes challenge the deleterious effects that gender-typed beliefs exert on people’s occupational aspirations and lifestyle choices. Surprisingly, however, the critical issue of how readily unexpected person-related knowledge can be acquired remains poorly understood. Accordingly, in two experiments in which the facial appearance of targets was varied to manipulate goodness-of-stereotype-fit (i.e., high vs. low femininity/masculinity), here we used a probabilistic selection task to probe the rate at which counter-stereotypic and stereotypic individuals can be learned. Whether occupational (Expt. 1) or trait-related (Expt. 2) gender stereotypes were explored, a computational analysis yielded consistent results. Underscoring the potency of surprising information (i.e., facial misfits), knowledge acquisition was accelerated for unexpected compared to expected persons, both in counter-stereotypic and stereotypic learning contexts. These findings affirm predictive accounts of social perception and speak to the optimal characteristics of interventions designed to reduce stereotyping outside the laboratory.

The efficacy and safety of levilimab (LVL) in patients with active rheumatoid arthritis (RA) has been confirmed in controlled clinical trials. This article presents the results of a preliminary analysis of a non-interventional observational study of LVL in RA patients. Objective: to evaluate the efficacy and safety of LVL in the treatment of patients with RA in real-world clinical practice. Materials and methods. The HELIOS study is a retrospective-prospective, multicenter, non-interventional study of retention rate of LVL therapy and the safety of LVL in patients with RA in real-world clinical practice. Patients received medical care, including LVL, according to routine clinical practice for the treatment of RA and Russian instructions for medical use of the drug. This article presents the results of an analysis of the efficacy and safety of LVL after 12 and 24 weeks of treatment. Efficacy was assessed using the DAS28-CRP/ESR, SDAI, CDAI and patient assessment of pain, fatigue and morning stiffness according to VAS (0–100 mm). Results and discussion. 524 patients from 42 medical centers in the Russian Federation were enrolled in the study from June 2022 to November 2023. The majority of patients were female (83.2 %) and the mean age of patients was 53 years. A statistically significant decrease in DAS28-CRP/ESR, SDAI, CDAI, patient assessment of pain, fatigue and morning stiffness (VAS) was observed after 12 and 24 weeks of treatment, regardless of previous treatment with biologics or Jak inhibitors (JAKi). LVL was well tolerated by patients, the most frequently reported adverse events were infections, changes in peripheral blood and laboratory abnormalities characteristic of treatment with IL-6R inhibitors. Conclusion. In real-world clinical practice, LVL has been shown to be highly effective and well tolerated in patients with RA when prescribed as the first biologic disease-modifying antirheaumatic drus (bDMARD) and after switching from other bDMARDs or JAKi.

Nuclear protein in testis carcinoma is a very rare but extremely aggressive highgrade carcinoma characterized by the presence of a fusion NUT gene – an oncogene. It is also called midline carcinoma because it mainly affects structures along the midline – head, neck, and lungs. We report a case of a woman with lung nuclear protein in testis carcinoma, diagnosed by bronchoscopic fibro-punch biopsy. The histological examination showed massive infiltration of bronchial wall of predominantly spindle-shaped neoplastic cells with unclear cytoplasmic borders. In some areas groups of rounded cells with clearly visible nucleoli and high mitotic rate were present. Foci with necrosis were also found. Immuno-histochemistry showed positive expression of cytokeratin, p63, CD56 and nuclear protein in testis antibodies and negative reaction for TTF1 and chromogranin A in neoplastic cells. The proliferative activity of tumor cells was very high (> 70%). Immunohistochemical study of the nuclear protein in testis expression is mandatory in cases with poorly differentiated lung tumors, with predominantly midline mass.

Abstract The tobacco alkaloid nicotine is known for its activation of neuronal nicotinic acetylcholine receptors. Nicotine is consumed in different ways such as through conventional smoking, e-cigarettes, snuff or nicotine pouches. The use of snuff has been associated with several adverse health effects, such as inflammatory reactions of the oral mucosa and oral cavity cancer. We performed a metabolomic analysis of nicotine-exposed THP-1 human monocytes. Cells were exposed to 5 mM of the alkaloid for up to 4 h, and cell extracts and medium subjected to untargeted liquid chromatography high-resolution mass spectrometry. Raw data processing revealed 17 nicotine biotransformation products. Among these, cotinine and nornicotine were identified as the two major cellular biotransformation products. The application of multi- and univariate statistical analyses resulted in the annotation, up to a certain level of identification, of 12 compounds in the cell extracts and 13 compounds in the medium that were altered by nicotine exposure. Of these, four were verified as methylthioadenosine, cytosine, uric acid, and l-glutamate. Methylthioadenosine levels were affected in both cells and the medium, while cytosine, uric acid, and l-glutamate levels were affected in the medium only. The effects of smoking on the pathways involving these metabolites have been previously demonstrated in humans. Most of the other discriminating compounds, which were merely tentatively or not fully identified, were amino acids or amino acid derivatives. In conclusion, our preliminary data suggest that some of the potentially adverse effects related to smoking may also be expected when nicotine is consumed via snuff or nicotine pouches.

Abstract A key factor affecting foam stability is the interaction of foam with oil in the reservoir. This work investigates how different types of oil influence the stability of foams generated with binary surfactant systems under a high salinity condition. Foam was generated with binary surfactant systems, one composed of a zwitterionic and a nonionic surfactant, and the other composed of an anionic and a nonionic surfactant. Our results showed that the binary surfactant foams investigated are more tolerant under high salinity conditions and in the presence of oil. This was visually observed in our microscopic analysis and was further attributed to an increase in apparent viscosity achieved with binary surfactant systems, compared to single surfactant foams. To understand the influence of oil on foam stability, we performed a mechanistic study to investigate how these oils interact with foams generated with binary surfactants, focusing on their applicability under high salinity conditions. The generation and stability of foam are linked to the ability of the surfactant system to solubilize oil molecules. Oil droplets that solubilize in the micelles appear to destabilize the foam. However, oils with higher molecular weights are too large to be solubilized in the micelles, hence the molecules will have less ability to be transported out of the foam, so oil seems to stabilize the foam. Finally, we conducted a multivariate analysis to identify the parameters that influenced foam stability in different oil types, using the experimental data from our work. The results showed that the oil molecular weight, interfacial tension between the foaming liquid and the oil, and the spreading coefficient are the most important variables for explaining the variation in the data. By performing a partial least square regression, a linear model was developed based on these most important variables, which can be used to predict foam stability for subsequent experiments under the same conditions as our work.

Abstract Heart failure remains a leading cause of mortality. Therapeutic intervention for heart failure would benefit from targeted delivery to the damaged heart tissue. Here, we applied in vivo peptide phage display coupled with high-throughput Next-Generation Sequencing (NGS) and identified peptides specifically targeting damaged cardiac tissue. We established a bioinformatics pipeline for the identification of cardiac targeting peptides. Hit peptides demonstrated preferential uptake by human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and immortalized mouse HL1 cardiomyocytes, without substantial uptake in human liver HepG2 cells. These novel peptides hold promise for use in targeted drug delivery and regenerative strategies and open new avenues in cardiovascular research and clinical practice.

BACKGROUND: Motor disorders of the upper limbs often develop after stroke. The use of traditional meth-ods to restore the motor functions of the upper limbs has limited effectiveness thus making the search and development of new rehabilitation approaches important. We propose to use a proactive selection of a purposeful movement as such an approach. AIM: to investi-gate the influence of different strategies of the upper limb movement regulation on the mo-tor decision making and hand kinematics parameters in stroke patients. METHODS: Ten pa-tients with stroke participated in the study during their hospital stay. They were divided into 2 groups and performed the task of selecting a movement target and performing arm movements for 10 sessions of 10 minutes each. The sessions were performed on separate days. When performing the task, patients selected one of the targets, either the near target or the distant one. The groups differed in the type of presentation of the distant target; the near target was stationary. The stimuli were presented on a touch screen arranged hori-zontally. A patient sat in front of the screen and placed the hand with a foam ball fixed in it on the starting area. The patient’s forearm was supported by means of a pendant. The pa-tient selected a target to reach in each attempt and then performed the movement by swip-ing the ball on the touch screen. The frequency of the target selection to perform the movement, the range of the selected target, the latencies of the movement onset, the hand speed and acceleration, and the accuracy in reaching the target were assessed. RESULTS: The results indicate that amidst the overall effects represented by a reduced movement on-set time [F (9.72)=8.59; p 0.001], a greater movement speed in reaching the distant tar-get [F (9.72)=2.79; p=0.007], a lower selection rate [F (9.72)=2.78; p=0.008] and a re-duced mean distance of the selected distant target [F (9.72)=2.19; p=0.033], the differ-ences in the distant target presentation between the groups have an impact on the hand movement dynamics in patients. Presenting a target at a random distance results in a greater selected target distance [F (1.8)=17.04; p=0.003], and an increased hand speed [F (9.72)=3.03; p=0.004] compared to the adaptive presentation. There is also a greater decrease in the movement onset time [F (9.72)=2.71; p=0.009] in the group of patients with the adaptive presentation of the distant target compared to the group with the random presentation. CONCLUSION: The differences in the target presentation strategy are reflected in the motor decision making and hand movement dynamics of stroke patients. A random-ized range of target presentation results in a higher amplitude arm movement closer to the activation threshold of the stretch reflex. The results of the study may be useful for selecting the rehabilitation strategies for stroke patients.

NiSpAR is a non-interventional, multicenter study whose aim was to describe a cohort of patients with non-radiological axial spondyloarthritis (nr-axSpA) and approaches to its diagnosis in the Russian Federation.Material and methods. The study involved 20 research centers in different regions of the Russian Federation. The work consisted of two phases: retrospective data collection 12 months before enrolment in the study and prospective observation of patients in whom the diagnosis of nr-axSpA was confirmed (104 weeks).The study included 272 patients who met the inclusion and exclusion criteria (Full Analysis Set, FAS). The mean age of the FAS-population was 38.7±11.0 years. The diagnosis of nr-axSpA was confirmed in 159 (58.5 %) of the 272 patients. Of the remaining 113 (41.5%) participants, 57 (50.4%) did not have the information required to confirm the diagnosis, 34 (30.1%) did not have pelvic radiographs, and 22 (19.5%) did not fulfil the ASAS criteria for nr-axSpA.Results and discussion. The mean age of patients with nr-axSpA was 37.6±10.4 years, more than half of them (52.8%) were women. The median disease duration was 36 [12; 80] months. In half of the patients the disease duration was more than 2 years, in more than one third – less than 2 years. The median CRP and ESR values were 5.0 [2.0; 12.0] mg/l and 11.0 [5.0; 18.0] mm/h, respectively. The BASDAI averaged 3.5±2.0 and was >4 in more than half of the cases (64.2%). The mean ASDAS-CRP value reached 2.6±1.1. Only 1 in 5 participants (20.8%) had low axSpA activity, while in 61.1% it was high (44.7%) or very high (16.4%). An inactive state was found in a small number of patients (9.4%). Twenty two (13.8%) patients had treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) in anamnesis, and 21 (13.2%) patients were still taking them.Conclusion. The results of the retrospective phase of the study show that in real-life clinical practice in the Russian Federation there is a continued positive trend towards improving the diagnosis of nr-axSpA. The median duration of the disease at the time of enrolment in the study was 3 years. The frequency of use of magnetic resonance imaging has increased by more than 1.8 times. At the same time, practitioners still have difficulties in establishing the diagnosis of nr-axSpA and a shortage of bDMARDs for treatment of these patients.

The progressive decline in the physiological functions during aging leads to various diseases that place a heavy burden on patients, their families and the society as a whole. Due to the increasing average life expectancy, the problems of prevention and treatment of age-related diseases are becoming more and more relevant. As a part of the research on the regulation of the aging program, considerable attention has been focused on a small family of NAD+-dependent deacetylases and deacylases called sirtuins. These proteins are involved in the regulation of numerous intracellular processes, and disruption of their functions plays an important role in the development of various diseases, such as metabolic disorders, pathologies of the cardiovascular system and other organs, musculoskeletal diseases, and neurodegeneration. It is interesting to note that the activity of sirtuins can be modulated to some extent under the influence of pharmacological agents, which makes them promising targets for the prevention and therapy of age-related diseases. The aim of the current review is to summarize the effects of sirtuins on the development and pathogenesis of neurodegenerative diseases, taking into account the reported clinical trials on the pharmacologic agents affecting the sirtuins’ activity.

Introduction: Tooth extraction is still one of the most common dental procedures, routinely performed for a variety of reasons. Tooth extraction forceps and elevators are well-known extraction instruments which have been the standard in tooth extraction procedures for well over a hundred years. Physics forceps are one possible alternative, aiming to perform less traumatic and more predictable extractions. Aim: The aim of study was to compare the effectiveness of physics forceps as an alternative, less traumatic, tool to the conventional extraction forceps. Materials and methods: All patients in the study were split into two groups: 26 patients in whom conventional extraction forceps were used (a control group) and 28 patients in whom we used physics forceps (a study group). For each group, we assessed the success of the extraction, the buccal cortical plate preservation, pain experience, and early wound healing. Results: There was no statistically significant difference in extraction success scores between the two groups. Physics forceps extractions preserved the buccal cortical plate in 81.1% of instances, while traditional forceps extractions did so in 71.8%. The patients in the study group reported less pain on the seventh day. At 10 days, the study group had a marginally higher proportion of completely healed extraction wounds. Conclusions: Atraumatic extractions preserve more hard and soft tissues at the extraction site. Physics forceps are a tool similar to the well-known conventional extraction forceps. They provide for somewhat better results in most extractions.

Introduction: In the period between 1997 and 2010, sibutramine-containing drugs were widely prescribed for obesity and over-weight management. Due to safety concerns, in 2010 all medicines containing sibutramine were urgently withdrawn from the USA and European pharmaceutical market. Although sibutramine is no longer available in pharmaceutical products, there have been numerous reports of mislabeled weight-loss dietary supplements containing sibutramine. Aim: This work aimed to develop and validate an accurate and sensitive high-performance thin-layer chromatographic method for the detection of sibutramine. Materials and methods: The method was developed using a CAMAG HPTLC system. Silica gel 60 F254 aluminum HPTLC plates were used as stationary phase and toluene:ethyl acetate:methanol (7:2:1 v/v/v) as mobile phase. Results: The calibration curve was built in the range of 0.250–1.250 μg/band. The method provided satisfactory linearity, specificity, precision, and accuracy. The LOD and the LOQ were 0.0765 μg/band and 0.2318 μg/band, respectively. Conclusions: The method allows for the simultaneous analysis of multiple samples as well as the rapid and sensitive monitoring of sibutramine levels in dietary supplements.

Extra-gastrointestinal stromal tumors arising from the pancreas are extremely rare. To date, just over 30 cases have been described in the world literature. A clinical observation of a 67-year-old patient with dull epigastric pain and a large cystic solid neoplasm instrumentally identified as an extra-gastrointestinal stromal tumor of the head of the pancreas is presented. The volume of surgical intervention consisted of pancreatogastroduodenectomy and right-sided hemicolectomy, since tumor invasion into the transverse mesocolon was detected intraoperatively. The final diagnosis of extra-gastrointestinal stromal sarcoma of the head of the pancreas with invasion into the mesocolon pT4N0M0, stage IIIb was made on the basis of histopathology and immunohistochemistry results. Extra-gastrointestinal stromal pancreatic tumors require careful differential diagnosis with other large abdominal masses. Timely diagnosis and use of modern treatment algorithms make it possible to avoid further disease progression.

Primary pulmonary synovial sarcoma is an extremely rare and aggressive neoplasm that primarily affects young people and has a poor prognosis. Establishing this diagnosis requires the exclusion of a wide number of other neoplasms with multimodal clinical, imaging, histological, immunohistochemical, and cytogenetic assessment. We present a case of synovial sarcoma of the left lung in a 44-year-old man, diagnosed immunohistochemically after left lower lobectomy with atypical resection of the 5th segment. Imaging, diagnostic workup, histological and immunohistochemical characteristics, surgical treatment, and prognosis are discussed.

Abstract A wide-field microscope with epi-fluorescence and selective plane illumination was combined with a single-photon avalanche diode (SPAD) array camera to enable live-cell fluorescence lifetime imaging (FLIM) using time-correlated single-photon counting (TCSPC). The camera sensor comprised of $$\text {192}\times \text {128}$$ 192 × 128 pixels, each integrating a single SPAD and a time-to-digital converter. Jointly, they produced a stream of single-photon images of photon arrival times with $$\approx \text {38 ps}$$ ≈ 38 ps accuracy. The photon arrival times were subject to systematic delays and nonlinearities, which were corrected by a Monte-Carlo algorithm. The SPAD camera was then applied to FLIM where histogramming the resulting photon arrival times in each pixel resulted in decays compatible with common data processing pipelines for fluorescence lifetime analysis. The capabilities of the TCSPC camera-based FLIM microscope were demonstrated by imaging living unicellular photosynthetic algae and artificial lipid vesicles. Epi-fluorescence illumination enabled rapid fluorescence lifetime imaging of living cells and selective-plane illumination enabled 3-dimensional FLIM of stationary samples.

Idiopathic clitoromegaly is a relatively rare disease. A case of isolated idiopathic clitoromegaly is presented. It concerns a 31-year-old woman, in whom the clitoris has showed a tendency for progressive enlargement in the last 3-4 years. The patient had no gynecological and systemic diseases and disorders. Karyotype and hormone levels were normal. No cystic changes in the ovaries and other changes in the abdominal organs were detected during ultrasound. Computerized axial tomographic (CAT) scan of the adrenal glands was performed and showed normal appearance. Method of selection in such cases is operative treatment – clitoroplasty with storage of neurovascular bundle of the clitoris.

Abstract Background Long-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections. Methods A prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the ‘exposed cohorts’ and ‘reference cohort’ was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC. Results Of 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final ‘matched’ analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3–120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9–21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts. Conclusions Wuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Introduction: Parkinson’s disease in its advanced stage is a progressive condition that can be treated with levodopa. The long-term complications of this treatment are difficult to manage. A new device-aided therapy has recently been developed to minimize these effects. Aim: The purpose of this study was to assess the efficacy and safety of the intestinal gel containing levodopa - carbidopa - entacapone, as well as to see if it had any impact on the disease’s non-motor symptoms. Additionally, we sought to identify the criteria for selecting among the various treatments that were offered. Materials and methods: This study includes the first five patients who started receiving the levodopa-carbidopa-entacapone gel for Parkinson’s disease in the Department of Neurology and Psychiatry at St Naum University Hospital for Active Treatment in Sofia, Bulgaria. To evaluate the influence of motor and non-motor symptoms of the disease, we used neurological examination and the Movement Disorder Society - Unified Parkinson’s Disease Rating Scale. The Parkinson’s Disease Quality of Life Questionnaire was used to assess the quality of life of the patients. Results: All patients showed improvement in their motor functions, quality of life, and sleep problems in comparison with those receiving oral levodopa. No patient experienced an increase in the dyskinesias. The postural stability continued to be impaired. For now, the medication has shown a protective effect against the levodopa-induced polyneuropathy. The main side effects were diarrhea and weight loss. Conclusions: Levodopa-carbidopa-entacapone therapy is a promising new modality of treatment for advanced Parkinson’s disease. The medication has been found to improve the patients’ motor functions and exert a positive effect on some non-motor symptoms. The drug has shown a good safety profile and tolerance. There is still a lack of clear criteria for choosing between the levodopa-carbidopa-entacapone and levodopa-carbidopa intestinal gels.

Background: Primary hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare tumour of vascular origin with an incidence of

The study of the young and old animals’ adaptation characteristics to the chronic effect of ethyl alcohol provides a quick solution of problems in biomedicine and gerontology, such as the formation of age related dependencies on pathologies. We studied the chronic effect of 15 % ethanol on young and old rats (3 and 20 month) of the Wistar line, which require free access to alcohol, for 160 days (5.3 months). The time of death occurrence, the relative mass dynamics of the liver, spleen and kidneys, the activity of alcohol dehydrogenase in the post-mitochondrial supernatant of liver, the content of carbonylated proteins and the activity of aconitate hydrotase in the mitochondria of the liver, as well as the serum creatinine level after 10, 20 and 40 days from the start of taking ethyl alcohol were determined. It was shown that the “initial” functional state of the increased activity elements in the formation of ethanol tolerance in young and old animals was different, this is evidenced by changes in the ratios of such indicators as: the relative mass of the liver, kidneys and spleen, the activity of alcohol dehydrogenase, aconitate hydrotase, the content of carbonylated proteins in the liver. We came to a combination that in young rats a “compensatory delayed” adaptation to the chronic effect of alcohol is realized, while (about 50 %) have a “compensatory delayed”, and the rest have a “pathogenetic” strategy; the choice of an adaptation strategy depends on the “initial” functional state, an extremely probable participation in the exchange of ethanol.

Abstract Economic costs of climate change are conventionally assessed at the aggregated global and national levels, while adaptation is local. When present, regionalised assessments are confined to direct damages, hindered by both data and models’ limitations. This article goes beyond the aggregated analysis to explore direct and indirect economic consequences of sea level rise (SLR) at regional and sectoral levels in Europe. Using a dynamic computable general equilibrium model and novel datasets, we estimate the distribution of losses and gains across regions and sectors. A comparison of a high-end scenario against a no-climate-impact baseline suggests a GDP loss of 1.26% (€871.8 billion) for the whole EU&UK. Conversely our refined assessments show that some coastal regions lose 9.56–20.84% of GDP, revealing striking regional disparities. Inland regions grow due to the displaced demand from coastal areas, but the GDP gains are small (0–1.13%). While recovery benefits the construction sector, public services and industry face significant downturns. We show that prioritising recovery of critical sectors locally reduces massive regional GDP losses, at negligible costs to the overall European economy. Our analysis traces regional economic restructuring triggered by SLR, underscoring the necessity of region-specific adaptation policies that embrace uneven geographic impacts and unique sectoral profiles to inform resilient strategy design.

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.

Cardiac implantable electronic devices (CIEDs) implantation procedure has a complication rate of 5-6% according to most studies. Lead perforation is a possible and serious adverse event which can present with a spectrum of symptoms from asymptomatic to sudden death. Diagnostic tools in case of suspected lead perforation are X-ray, transthoracic echocardiography, pacemaker interrogation and computed tomography with the last one being the gold standard. Lead extraction could be done endovascularly or surgically. Transvenous removal is a possible option for active fi xation leads, while removal of passive fi xation leads is preferably done surgically, because of the bulky tip of the lead, which could damage the heart chambers and the vessels. In this article, we present a case of a massive ventricular perforation from a passive fi xation lead, further complicated by a cardiac tamponade. Surgical removal was the treatment of choice with subsequent implantation of a permanent dual-chamber pacemaker.

We describe a rare case of asynchronous bilateral carcinoma of the mammary glands in a 66-year-old man. The patient was admitted to the Department of Dermatology and Venereology due to exacerbation of chronic eczema. During the examination, a 3×2-cm tumor with retraction of the mammilla was found in the right mammary gland. Mastectomy and regional lymphatic dissection were performed. Histological examination showed invasive ductal carcinoma, ER (+) 70%, PR (−), HER2 (−). Treatment included chemotherapy, radiotherapy, and hormone therapy. Three years later, the patient reported a lump in the left breast. The presence of a tumor formation was confirmed by mammography and ultrasound examination. A radical mastectomy with regional lymphatic dissection was performed. Histological examination showed invasive ductal carcinoma of the mammary gland, ER (3+) 80%, PP (2+) 60%, HER2 (+++), and Ki67 (+) 80%. Treatment with chemotherapy and radiation therapy was carried out. Five years after diagnosis of the second carcinoma, the patient is in a good general condition. Regardless of its rarity, the described case should draw doctors’ attention to this pathology. Assessment of risk factors and periodic breast examination in men would allow early diagnosis, timely treatment, and better prognosis of the disease.

The objective of this study was to present a comparative analysis of the antimicrobial activity of methanolic leaf extracts from seven Juniperus L. species, together with a tentative analysis of their total flavonoid and o-dihydroxyphenolic acids content. The chemical analyses were performed by colorimetric methods and the antimicrobial activity was assessed via broth microdilution. The studied extracts showed total content of o-dihydroxyphenols in the range of 26 to 34 µg of caffeic acid equivalent/mg DE and total flavonoid content of 13 to 24 µg of quercetin equivalent/mg DE. The sensitivity of Gram-positive bacteria to the studied extracts differed significantly with the following order of activity: J. sabina var. balkanensis > J. communis ‘Laxa’ > J. formosana > J. pinchotii > J. ashei > J. excelsa ≈ J. sibirica. Weak activity was observed for all extracts against Gram-negative bacteria and Candida strains. The analysis of the MBC/MIC ratio showed that the extracts exhibited bactericidal effect against Gram-negative bacteria (MBC/MIC≤4), while bactericidal or bacteriostatic action (MBC/MIC>4) was determined towards Gram-positive bacteria. Moreover, these extracts showed fungicidal (MFC/MIC≤4) or fungistatic effect (MFC/MIC>4). Best antibacterial activity was registered for the J. sabina var. balkanensis leaf extract. The multivariate data analyses were carried out by SIMCA 16 (v16.0.2) software. The hierarchical cluster analysis and principal component analysis, based on phytochemical and antimicrobial data, classified the studied juniper species into four groups: 1. J. ashei; 2. J. excelsa, J. sibirica; 3. J. sabina var. balkanensis, J. communis Laxa, J. formosana; 4. J. pinchotii.

Scientific relevance. The number of live bacteria is a quality parameter controlled at all stages of live plague vaccine production. Currently, live microbial cell counting uses a bacteriological method. However, flow cytometry has the potential to increase analytical accuracy and reduce testing time.Aim. This study aimed at testing the applicability of flow cytometry to assessing the quality of live plague vaccines.Materials and methods. The study quantified live microbial cells in 5 experimental batches of live plague vaccine as part of their quality control using the bacteriological method according to the State Pharmacopoeia of the Russian Federation (FS.3.3.1.0022.15). Cytofluorometry of the samples used the SynaptoGreen fluorescent dye.Results. The study quantified live microbial cells in live plague vaccine samples using the bacteriological method and flow cytometry. The results obtained by the bacteriological method ranged from 27.8±2.2 to 56.5±3.1% with an average of 39.8±5.4%. The results obtained by flow cytometry ranged from 29.2±1.2 to 59.1±2.1% with an average of 41.7±5.5%. The statistical analysis showed no significant difference between the results of vaccine quality control by both methods, as well as a high coefficient of determination.Conclusions. The results show that flow cytometry is an appropriate method for the quantification of live microbial cells as part of the quality control of plague vaccines. Being quick, easy, and highly informative, flow cytometry is preferable to traditional methods.

Lyme borreliosis (LB), a tick-borne infection caused by bacteria in the Borrelia burgdorferi sensu lato complex, is increasingly prevalent on the Balkan Peninsula, including Bulgaria, where it is the most common tick-borne disease. This study aimed to assess the seroprevalence of LB across Bulgaria by analyzing 1892 serum samples for specific IgG antibodies using a two-tier testing protocol involving an ELISA and immunoblot methods. The results revealed an overall seroprevalence rate of 5.4%, with significant variation based on age, sex, and residence. Seroprevalence increased with age, peaking at 8.4% in individuals over 65 years. Males had a seroprevalence of 8.4% compared to 3.3% in females, and rural residents showed higher seroprevalence (10.2%) compared to urban residents (4.4%). Regional analysis indicated that seroprevalence ranged from 0.0% to 20.0%, with higher rates in northern provinces such as Gabrovo (18.9%) and Targovishte (20.0%). This study highlights the importance of two-step testing protocols for accurate diagnosis and underscores the need for increased awareness and further research to enhance public health measures and the management of LB in Bulgaria.

Background: Menstruation is a central part of the everyday life of most women, and menstrual attitudes may impact health and well-being. Objectives: This article aimed to map menstrual attitudes among adult women and examine factors associated with these attitudes, such as aspects of menarche and current menstruation, and rarely studied factors, such as genital self-image and sexual openness. Study Design: A cross-sectional online survey. Method: A sample of 1470 women, aged 18–50 years, were recruited through social media sites. The Menstrual Self-Evaluation Scale was used to measure three different attitudes: menstruation as natural, shameful, and bothersome. Multiple linear regression analysis was used to investigate the relationship between each attitude and factors related to menarche and current menstruation, contraceptive use, genital self-image (assessed by Female Genital Self-Image Scale ), and sexual openness ( Personal Comfort with Sexuality Scale ). Sociodemographic variables were included into the models as covariates. Results: Agreeing with the attitude of menstruation as something natural was predicted primarily by positive emotions at menarche, experiencing less menstrual pain, using no or nonhormonal contraception, and having a positive genital self-image. Perceiving menstruation as bothersome was predicted by a lower educational level, experiencing stronger menstrual pain, having more perimenstrual psychological symptoms, and using hormonal contraceptives. Menstruation as something shameful was chiefly predicted by lower sexual openness and a negative genital self-image. Conclusion: Many women held attitudes about menstruation as both something natural and bothersome. Menarche and current menstruation experiences, and contraceptive method, played central roles in shaping attitudes toward menstruation as natural and bothersome. Viewing menstruation as shameful stood out from other attitudes by indicating a triad of self-objectified shame that includes menstruation, sexuality, and genital self-image. Further research into the relationships between menstruation, contraceptive use, sexuality, and body image is needed to enhance our understanding of women’s menstrual health.

Background. Modern breast cancer chemotherapy regimens (BC) consider individual patient parameters and ranges of cardiotoxic doses. However, clinicians often record clinical and laboratory-instrumental signs of cardio- and vasculotoxicity in patients, which emphasizes the high importance of searching for markers of early toxic response. Aim. To study the characteristics of the response of arterial stiffness on the background of anthracycline-containing chemotherapy to determine potential markers of vasculotoxicity in BC patients. Materials and methods. 20 women with a BC were included. The patients received 4 cycles of chemotherapy in the doxorubicin + cyclophosphane (AC) regimen with an interval of 23 weeks, then they were injected with paclitaxel weekly for 12 injections, or docetaxel once every 3 weeks. All patients underwent TTE, arterial stiffness determination by the "gold standard" method and using volumetric sphygmography before the start of treatment, after the completion of the anthracycline component and after the end of taxanes. Results. The average age of the patients was 45.55.31 years. After completing the course of anthracyclines, there was a significant increase in heart rate (from 65.69.3 to 73.310.1 beats/min.), a decrease in SBP (from 122.69.9 to 116.512.3 mmHg) and DBP (from 78.98.5 to 76.28.6 mmHg), a decrease in carotid femoral pulse wave velocity (cfPWV) (from 9.321.41 to 7.851.57 m/s), CAVI index on the left (from 6.780.81 to 6.50.88), the velocity of the cardio-ankle pulse wave on the right and left (from 6.70.6 to 6.50.7 m/s; from 7.00.6 to 6.30.8 m/sc, respectively). After the completion of the taxane, there was a tendency to increase these indicators, however, they remained significantly lower compared to the values before the start of treatment. Conclusion. A comparative analysis of arterial stiffness indicators at different stages of chemotherapy showed a more pronounced reaction of cfPWV, CAVI, cardio-ankle pulse wave to the administration of anthracyclines, which presumably may be associated with concomitant hemodynamic restructuring.

Paraganglioma is a neuroendocrine tumor that originates from extraadrenal chromaffin cells. Primary thyroid paraganglioma is an extremely rare neoplasm. In this study, an exceptionally uncommon case of recurrent mediastinal malignant paraganglioma with primary origin from thyroid gland is presented. Median resternotomy, resection of left brachiocephalic vein, and extirpation of the mediastinal tumor were performed successfully. Commonly, it is preoperatively misdiagnosed and has unpredictable biological behavior. Incorrect diagnosis results in disastrous consequences for the patient, and consequently, correct pre- and postoperative diagnoses promise an optimal treatment plan and good prognosis. Long-term follow-up is indicated in all patients due to the risk of recurrence and distant metastases.

Aspergillosis is a fungal infection, caused by the mould Aspergillus, most commonly Aspergillus fumigatus species. Chronic pulmonary aspergillosis after SARS Cov-2 infection is a rare presentation that is commonly misdiagnosed. The prolonged corticosteroid and antibiotic application and the pro-inflammatory state in COVID-19 patients predisposes to Aspergillus infection and its chronification. Surgery plays a pivotal role in cases with unclear diagnosis, ineffective medical therapy or when complications develop. We present a case of a 73-year-old woman with chronic pulmonary aspergillosis, developed after COVID-19 pneumonia. A right lateral muscle-sparing thoracotomy, right upper lobectomy and atypical resection of the 9th and 10th segments were performed.

The Human Major Histocompatibility Complex (HLA) is the most polymorphic region of the human genome and encodes molecules with a central role in antigen-specific immune responses. Class I and class II HLA genes have an important role in bone marrow and solid organ transplantations. HLA typing by Next Generation Sequencing (NGS) provides unambiguous second field or allelic level resolution and, therefore, better matching of donor and recipient and a higher chance of survival for transplanted patients. The aim of this study was to validate GenDx NGS HLA typing protocol for 6 HLA loci (HLA-A, -B, -C, DRB1, -DQB1 and DPB1).

The failure of heart valve bioprostheses, requiring repeated intervention to replace them, is a serious drawback that narrows the scope of such devices. The present study demonstrates the experimental investigation of a medical device designed to partially solve the problem of repeated interventions on heart valves, primarily with an emphasis on reducing the duration and trauma of such procedures due to the sutureless balloon implantation method of the «valvein- valve» method.Material and methods. The paper presents a series of in silico, in vitro and in vivo experiments to evaluate various aspects of the device under development. Numerical modeling of the final shape setting to the supporting frame of the heart valve prosthesis to select the most promising concept for prototyping was carried out in the Abaqus/CAE (Dassault Systèmes, France) based on the finite element method. The selected optimal support frame model was prototyped in the form of a series of prosthesis samples of four standard sizes for hydrodynamic studies of quantitative characteristics in vitro. The study was carried out in the Vivitro Labs unit (Vivitro Labs, Canada), imitating the physiological mode of the heart, the prostheses were examined for the mitral position. The developed prototypes of the device were supplemented with related products, an implant holder and a balloon catheter, after which the proposed method of sutureless fixation was validated in an in vitro implantation procedure on a bovine heart model and a series of in vivo (n = 3) chronic experiments on animals.Results. In the course of numerical simulation, it was shown that in Model No. 3 of the supporting frame of the prosthesis, the smallest stresses occur – with an amplitude of up to 490 MPa. For other concepts (Models No. 1 and No. 2), this indicator was significantly higher, 543 and 514 MPa, respectively. Prototypes obtained on the basis of the selected shape of the support frame demonstrated satisfactory hydrodynamic characteristics: effective hole area 190-261 mm2, regurgitation volume 6–9 ml/cycle, average transprosthetic gradient 4.4–6.4 mmHg, depending on size. The study of the technology of sutureless balloon implantation in an in vitro model of the heart and the subsequent chronic experiment on sheep confirmed the main idea of the system – the possibility of a significant reduction in the duration of repeated prosthetics. It has been shown that the time of suture implantation of the “classic” frame prosthesis of the mitral valve is 23–29 minutes, with a total access time of 41–52 minutes. When implanting the experimental device, the sutureless prosthesis itself took 4–6 minutes, access time 24–29 minutes. At the same time, one-month results of an echocardiographic study of the operation of the prosthesis demonstrated satisfactory hemodynamics.Conclusions. This work demonstrates a consistent series of tests of the system being developed for repeated heart valve replacement, which substantiates some design solutions, confirms the effectiveness and viability of the chosen approach to sutureless minimally invasive implantation.

Abstract A combination of a high sediment input and intense bottom currents often leads to the formation of contourites (sediments deposited or significantly reworked by bottom currents). Both of these components are present in the Vema Fracture Zone valley which is the most important passageway for the distribution of the Antarctic Bottom Water from the West to the North-East of the Atlantic. However, no contourite drifts, moats or contourite channels have been found in this region in more than half a century of research. The prevailing sedimentation paradigm postulates that turbidity currents have predominantly governed sedimentation in this region during the Pleistocene. This work describes the first example of contourite depositional system identified in the Vema Fracture Zone. The discovery was made through detailed high-resolution sub-bottom profiling, as well as numerical modeling and direct measurements of bottom current velocities. Such systems are exceptionally uncommon in fracture zones. This study highlights the importance of further research of contourites along the Vema Fracture Zone based on modern concepts of contourite and mixed depositional systems. The work also emphasizes the need to reevaluate the impact of bottom currents on sedimentation in this region, and particularly in the narrow segments of the fracture zone valley.

Species belonging to the genus Salvia, Lamiaceae, have been deeply involved in the folk medicine of different nations since ancient times. Lilac sage, or Salvia verticillata L. (S. verticillata) is a less studied species from the genus. However, it seems to have a prominent potential for the future drug discovery strategies of novel phytopharmaceuticals. This review aims to summarise the data on the biological activity and the phytochemical profile of extracts and essential oils derived from S. verticillata. This review is based on data from 57 in vitro and in vivo studies. The chemical profile of S. verticillata includes different synergic compounds like phenolic acids, flavonoids, terpenes, and salvianolic acids. Although some small amounts of salvianolic acid B were found in S. verticillata extracts, the major compound among the salvianolic acids is salvianolic acid C, a compound associated with the potential for improving liver fibrosis, cardio- and hepatoprotection, and the inhibition of SARS-CoV-2 infection. The cannabinoid type 2 receptor agonist β-caryophyllene is one of the major compounds in S. verticillata essential oils. It is a compound with a prominent potential in regenerative medicine, neurology, immunology, and other medical fields. The in vivo and the in vitro studies, regarding S. verticillata highlighted good antioxidant potential, anti-inflammatory, antibacterial, and antifungal activity. S.verticillata was also reported as a potential source of drug candidates for the treatment of neurodegenerative diseases such as Alzheimer’s disease, because of the inhibitory activity on the acetylcholinesterase. However, the number of studies in this direction is limited.

In this study, UHPLC-HRMS analysis of the defatted methanol extract obtained from Inula salicina L. led to the identification of 58 compounds—hydroxycinnamic and hydroxybenzoic acids and their glycosides, acylquinic and caffeoylhexaric acids, and flavonoids and their glycosides. In addition, a new natural compound, N-(8-methylnepetin)-3-hydroxypiperidin-2-one was isolated and its structure was elucidated by NMR spectroscopy. The presence of a flavoalkaloid in genus Inula is described now for the first time. Chlorogenic acid was the main compound followed by 3,5-, 1,5- and 4,5-dicaffeoylquinic acids. The methanol extract was studied for its antioxidant potential by DPPH, ABTS, and FRAP assays and sun protective properties. In addition, a study was conducted to assess the effectiveness of the tested extract in inhibiting biofilm formation by Gram-positive and Gram-negative strains. Results from crystal violet tests revealed a notable decrease in biofilm mass due to the extract. The anti-biofilm efficacy was confirmed through the observation of the biofilm viability by live/dead staining. The obtained results showed that this plant extract could be used in the development of cosmetic products with antibacterial and sun protection properties.

The widespread use of the oral poliovaccine from Sabin strains (tOPV) radically reduced poliomyelitis incidence worldwide. However, OPV became a source of neurovirulent vaccine-derived polioviruses (VDPVs). Currently, circulating type 2 VDPVs (cVDPV2) are the leading cause of poliomyelitis. The novel OPV type 2 vaccine (nOPV2), based on genetically modified Sabin strain with increased genetic stability and reduced risk of cVDPV formation, has been used to combat cVDPV2 outbreaks, including one in Tajikistan in 2021. In order to identify the importation of cVDPV2 and nOPV2-derivates, stool samples from 12,127 healthy migrant children under 5 years of age arriving from Tajikistan were examined in Russia (March 2021–April 2022). Viruses were isolated in cell culture and identified via intratype differentiation RT-PCR, VP1 and whole-genome sequencing. cVDPV2 isolates closely related with the Tajikistan one were isolated from two children, and nOPV2-derived viruses were detected in specimens from 106 children from 37 regions of Russia. The duration of nOPV2 excretion ranged from 24 to 124 days post-vaccination. nOPV2 isolates contained 27 mutations per genome (0.36%) on average, with no critical genetic changes, which confirms the genetic stability of nOPV2 during field use. The possibility of epidemiologically significant poliovirus introduction into polio-free countries has been confirmed. The screening of special populations, including migrants, is required to maintain epidemiological well-being.

The development of a safe and effective vaccine against avian influenza A virus (AIV) H5N8 is relevant due to the widespread distribution of this virus in the bird population and the existing potential risk of human infection, which can lead to significant public health concerns. Here, we developed an experimental pVAX-H5 DNA vaccine encoding a modified trimer of AIV H5N8 hemagglutinin. Immunization of BALB/c mice with pVAX-H5 using jet injection elicited high titer antibody response (the average titer in ELISA was 1 × 105), and generated a high level of neutralizing antibodies against H5N8 and T-cell response, as determined by ELISpot analysis. Both liquid and lyophilized forms of pVAX-H5 DNA vaccine provided 100% protection of immunized mice against lethal challenge with influenza A virus A/turkey/Stavropol/320-01/2020 (H5N8). The results obtained indicate that pVAX-H5 has good opportunities as a vaccine candidate against the influenza A virus (H5N8).

Objective: This study aimed to explore the diagnostic role of D-dimers and ferritin in ascitic fluid. We analyzed ascitic and blood samples from twenty cirrhotic patients, using the Child-Pugh classification to assess liver cirrhosis severity. Methods: Blood tests evaluated platelets, albumin, INR, fibrinogen, CRP, ferritin, and D-dimers, while ascitic fluid analysis incorporated total protein, albumin, LDH, cholesterol, leukocytes, with a focus on D-dimers and ferritin.