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Fundamental and Clinical Medicine

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Vol 9, No 3 (2024)
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EDITORIAL

ORIGINAL RESEARCH

8-18 218
Abstract

Aim. To assess the risk of malignant central nervous system (CNS) tumors among the first-generation offspring of workers from the Mayak Production Association.

Materials and Methods. A retrospective epidemiological analysis was conducted in a cohort of the offspring of workers from Russia's first nuclear power plant (n = 8890), born between 1949 and 1973. The comparison group consisted of 4345 offspring born during the same period to non-exposed parents. The observation period covered 72 years (1949−2020), with a total of 818,208 person-years of follow-up. The analysis focused on the frequency, dynamics, and structure of CNS malignancies. The relative risk of CNS tumors and the excess relative risk per unit dose of parental occupational radiation exposure were calculated with 95% confidence intervals.

Results. Overall, the frequency of CNS tumors in both groups over the entire observation period did not differ significantly (3.4 per 1000 in the main group, 1.8 per 1000 in the comparison group). Analysis of CNS tumor incidence dynamics across calendar periods showed no significant differences, with the peak in the main group occurring during 2001−2010. No significant differences were found in the age of CNS tumor onset or the average age of parents at the time of offspring birth. Histological structure and localization of CNS tumors varied across groups. The relative risk assessment for CNS tumors showed a statistically insignificant increase in risk among the offspring in the main group when considering total observations and sex-specific analyses. Among the offspring of mothers with confirmed preconceptional and intrauterine occupational radiation exposure, the relative risk of CNS tumors was higher for males and both sexes combined (3.6 [1.06−12.28] and 2.74 [1.08−6.93]; 4.34 [1.27−14.77] and 3.3 [1.31−8.36], respectively). However, the analysis of excess relative risk did not indicate significant risk estimates for maternal radiation exposure, neither in general nor across different dose intervals.

Conclusion. The study did not confirm the hypothesis that parental occupational radiation exposure influences the risk of CNS tumors in offspring. Given the relatively young age of the cohort and the low number of CNS tumor cases, issues related to maternal radiation exposure require further observation.

19-28 264
Abstract

Aim. To determine the cytocompatibility of carbon-carbon composite materials (CCCM) and assess their ability to be impregnated with vancomycin.

Materials and Methods. The study included samples of carbon-carbon composite materials (CCCM). The cytocompatibility of CCCM blocks was evaluated using a culture of eukaryotic cells (Vero cell line). Biofilms of S. aureus ATCC 29213 (MSSA), S. aureus ATCC 43300 (MRSA), S. epidermidis ATCC 12228 (MSSE), and S. epidermidis ATCC 29887 (MRSE) were formed by immersing sterile test samples of CCCM into a nutrient medium which contained bacteria. After 24-hour incubation, the samples were washed, placed in an ultrasonic bath, and sonication fluid was inoculated using the sector method. To saturate the CCCM blocks with antibiotics, they were placed into a vancomycin solution and then lyophilized under negative pressure with gradual heating. The antimicrobial activity of the resulting blocks was studied using the cup plate method against the same reference cultures of staphylococci. The dynamics of vancomycin elution from CCCM was investigated using high-performance liquid chromatography.

Results. Vero cells maintained their viability in the presence of the tested material. Considering the highly porous structure of CCCM and variable diameter of the pores, we suggested a good osteointegration potential of this material. On the samples without an impregnation with an antibacterial drug, reference strains of staphylococci were able to form a biofilm with a sufficient number of bacterial cells to initiate an infectious process. The duration of antimicrobial activity of the antibioticim-pregnated samples against the reference staphylococcal strains was up to 3 days. The majority of the antibiotic eluted from the CCCM into the incubation medium during the first two days.

Conclusion. The cytocompatibility and porosity of CCCM in combination with a vancomycin impregnation makes this material promising for the fabrication of implants with antimicrobial activity as well as tissue engineering constructs.

29-38 165
Abstract

Aim. To evaluate changes in nutritional status parameters among the adult population of the Omsk region during.

Materials and Methods. The comparison of nutritional status parameters was conducted as a part of an experimental epidemiological study using a "before-after" design. The intervention consisted of activities carried out in the region from 2019 to 2023 under the federal project "Strengthening Public Health." In 2018, a representative sample (n = 241) was formed, stratified by age, gender, and residential area; in 2023, a similar sample (n = 506) was used. Nutritional status was assessed using somatometric, clinical, and laboratory methods.

Results. We have documented a significant reduction in the prevalence of severe obesity (grades II-III, from 7.1 ± 1.1% to 2.4 ± 0.9%), and a trend towards a decrease in prevalence of underweight (from 5.4 ± 1.4% to 3.0 ± 0.8%; p = 0.078). In 2023, the proportion of individuals with overweight was 36.0 ± 2.1%, and 16.4 ± 2.4% of the adult population suffered from obesity. The prevalence of micronutrient deficiencies decreased significantly (p < 0.001). In 2023, deficiencies in vitamin D (61.8 ± 1.7%), folates (50.0 ± 3.2%), vitamins B1 (26.6 ± 2.8%), B6 (36.7 ± 3.1%), and E (28.5 ± 2.9%), magnesium (32.0 ± 2.0%), zinc (27.2 ± 2.8%), copper (36.0 ± 3.1%), iron (25.0 ± 1.7%), and selenium (31.2 ± 3.9%) were the most common. Compared to 2018, the prevalence of deficiencies in vitamins D, E, B1, B6, and folates significantly decreased (p < 0.05), while the provision of essential elements remained unchanged.

Conclusion. The prevalence of various nutritional disorders among the adult population of the Omsk region reduced, as the implementation of the federal project «Strengthening Public Health» under the national project "Demography" improved the provision of vitamins.

39-46 217
Abstract

Aim. To characterize micronutrient homeostasis in women with a combination of gestational diabetes mellitus (GDM) and subclinical hypothyroidism (SCH), and to determine the significance of micronutrient imbalance in complicated pregnancies.

Material and Methods. The study analyzed 439 birth histories of patients with GDM and SCH, who underwent plasma micronutrient analysis at 12−13 weeks of gestation. The study examined the patients' anthropometric and medical history data, complications during the current pregnancy, the timing and method of delivery, and newborn conditions. Some of these indicators were compared with previously obtained plasma micronutrient levels (Al, Co, Cu, Fe and others) measured at 12−13 weeks of gestation.

Results. The analysis of micronutrient concentrations in plasma at 12−13 weeks of gestation revealed iron deficiency in 250 patients (57%), iodine deficiency in 231 patients (52.6%), cobalt deficiency in 229 patients (52.2%), vitamin B12 deficiency in 285 patients (64.9%), and vitamin D deficiency in 280 patients (63.6%). Iron deficiency was significantly more common in pregnant women with overweight and obesity than in those with normal body weight (χ2 =.14 and 5.32, respectively). The risk of developing iron deficiency also increased with higher body weight (1.81-fold for overweight (95% CI 1.2–2.73) and 2.07-fold for obesity (95% CI 1.11–3.86). Around 50% of patients with threatened preterm birth had cobalt deficiency and 59% of patients with anemia had iron deficiency. Selenium, calcium, and vitamin B12 deficiencies were observed in 55%, 70%, and 73% of patients with preeclampsia (PE), respectively.

Conclusion. The observed deficiency of certain micronutrients in specific pregnancy complications suggests that correcting micronutrient levels during pre-conception or early gestation may improve pregnancy outcomes.

47-56 175
Abstract

Aim. To evaluate the effectiveness of long-term (five-year) supervised physical exercise in patients with chronic heart failure (CHF) following myocardial infarction (MI) and type 2 diabetes mellitus (T2DM).

Materials and Methods. The study included 88 patients with CHF of functional class II-III after MI and concomitant T2DM. In addition to standard medication therapy, patients in the main group (n = 42) performed regular moderate-intensity physical exercises for 30−60 minutes at least 5 days a week. The control group consisted of 46 patients who received standard medication therapy. Patients in both groups had similar clinical and demographic characteristics. After 5 years of follow-up, we assessed the incidence of a composite endpoint (death, MI, emergency myocardial revascularization, acute CHF decompensation), quality of life (measured by the SF36 questionnaire), levels of anxiety and depression (measured by the HADS questionnaire), and levels of fatigue (measured by the MFI-20 questionnaire). By the end of the five-year observation period, data were available for 40 patients in the main group (11 patients were excluded from the study due to discontinuation of regular physical exercise) and 42 patients in the control group.

Results. The incidence of the composite endpoint was 55.2% and 80.9% in main and control group, respectively (p = 0.038). Regular physical exercise over the five-year period was associated with a higher quality of life according to the SF36 questionnaire (64.5 [63.1; 67.8] vs. 49.2 [48.4; 49.8], p = 0.001), lower levels of anxiety (5.8 [5.1; 7.7] vs. 8.0 [6.8; 9.2], p = 0.042) and depression (2.9 [2.2; 4.2] vs. 10.7 [10.5; 12.3], p = 0.001) according to the HADS questionnaire, and lower levels of general fatigue according to the MFI-20 questionnaire (9.1 [8.5; 11.2] vs. 15.1 [14.5; 15.4], p = 0.019).

Conclusion. Long-term regular physical exercise in patients with CHF and T2DM improves cardiovascular outcomes and psychological status of patients.

57-65 212
Abstract

Aim. To assess the impact of adherence to various outpatient rehabilitation programs during the first three months after coronary artery bypass grafting (CABG) on the development of cardiovascular events over four years of follow-up.

Materials and Methods. The study evaluated the influence of adherence to outpatient cardiac rehabilitation programs on the incidence of cardiovascular events in patients following open coronary artery revascularization surgery. Adherence to cardiac rehabilitation was assessed over a threemonth period, and the observation period for cardiovascular events extended to four years from the time of the surgery.

Results. During the first year of observation, we did not find significant differences in the effectiveness and safety of outpatient cardiac rehabilitation programs. However, we revealed statistically significant differences in the patient adherence to physical training. Over the four-year observation period, a higher number of cardiovascular events were recorded in the group of patients who were non-adherent to physical training. Statistically significant differences were observed with regards to the incidence of myocardial infarction and cardiovascular death.

Conclusion. Adherence to recommendations following open revascularization procedures is crucial for the prognosis of myocardial infarction and cardiovascular death. Modern methods of providing medical care in the outpatient phase of cardiac rehabilitation enable patients to engage in effective and safe physical training comparable to those conducted in specialized cardiac rehabilitation facilities under the direct supervision of medical personnel.

66-73 176
Abstract

Aim. To identify the characteristics of pregnancy and childbirth in women with endometriosis-associated infertility (EAI).

Materials and Methods. Here we performed retrospective case-control study which included 115 women with histologically verified endometriosis and 250 women without this condition. Statistical analysis was conducted using the IMB SPSS Statistics 20 software package. The data distribution was assessed using the Kolmogorov-Smirnov test. Quantitative data are presented as median (Me) and interquartile range (Q1 – Q3) using the Mann-Whitney test. The level of statistical significance for testing the null hypothesis was set at p < 0.05.

Results. Pregnancy in patients with EAI was statistically significantly more often complicated by placenta previa compared to the control group: 6 (5.2%) versus 3 (1.2%) (p = 0.031). Patients with EAI were delivered via cesarean section in 49.6% of cases, compared to 13.2% in those without EAI (p < 0.001). Labor in women with EAI was statistically significantly more often complicated by uterine inertia (hypotonic labor, 7.0% versus 2.4% in those without EAI, p = 0.043), retained placenta (4.3% vs 0.4%, p = 0.013); and hypotonic bleeding (3.5% vs 0.4%, p = 0.036). Maternal and neonatal outcomes including birth weight, Apgar scores at 1 and 5 minutes, and the duration of hospital stay did not differ significantly between the groups.

Conclusions. Patients with EAI are characterized by a complicated course of pregnancy and childbirth with a higher incidence of placenta previa, abnormal labor, hypotonic bleeding, retained placenta, and cesarean delivery. Hence, the development of respective therapeutic and preventive measures is required to prevent these complications.

74-85 155
Abstract

Aim. To identify the most suitable pathogenetic mechanisms for in-depth study of the antitumor and antimetastatic effects of tested hybrid organotin compounds using the immunohistochemical approach.

Materials and Methods. Here, we tested bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (laboratory code Me-3), belonging to the class of hybrid organotin compounds, on 30 female C57Bl/6 mice using a universal model of transplantable tumors with spontaneous metastasis (B16 melanoma). 48 hours after tumor cell transplantation, we intraperitoneally administered Me-3 once daily to female C57Bl/6 mice for 10 days at a total dose (TD) of 375 mg/kg. For histological analysis, we used the primary tumor node of B16 melanoma. Immunophenotyping of B16 melanoma tissue samples was carried out using the polyclonal antibodies to transforming growth factor beta 1 (TGFβ-1), vascular endothelial growth factor A (VEGFA), Bcl2-associated X Protein (Bcl-2), cluster of differentiation 34 (CD34).

Results. After the exposure to Me-3, we found a reduced immunohistochemical signal to TGF-β1 and Bcl-2 3 in the tumor tissue. Low doses of Me-3 have also impacted angiogenesis.

Conclusion. Me-3 has a pro-apoptotic and anti-angiogenetic effects on B16 melanoma cells in C57Bl/6 mice.

REVIEW ARTICLES

86-97 156
Abstract

Here we review the role of innate and adaptive immunity at ascending lung cancer stages in smoking and non-smoking patients. T cell activity and the expression of pro-inflammatory cytokines were found to be elevated in smokers. As a consequence, smoking has been identified as a significant risk factor promoting lung carcinogenesis. Further experimental research in this area will allow the development of novel diagnostic approaches, including circulating biomarkers and personalised medicine.

98-108 219
Abstract

Immune cells, cytokines, and interferons are key mediators that ensure the gestational process from implantation to childbirth. The coordination of their signaling pathways determines molecular interactions between the mother and the fetus, the physiological course of pregnancy and its outcomes, particularly in the context of maternal respiratory viral infections. Here we analyze current information on physiological and pathological roles of cytokines and interferons during gestation in both uncomplicated and complicated pregnancies. Disrupted cytokine signaling might significantly alter fetal and placental development, leading to pregnancy complications and birth defects.

109-119 219
Abstract

Agent-based simulation modeling provides additional opportunities to study the patterns of pathogen spread among populations, taking into account the complexity and stochasticity of the epidemic process. Agent-based modeling is considered as a computational approach in which agents with predefined characteristics can interact with each other and with the environment according to pre-specified rules. Here I consider the historical background of agent-based modeling in the field of infectious diseases, describe the basic definitions and classifications, and discuss strengths and weaknesses of agent-based modeling. The article details four interconnected main components that are subject to modeling: disease features (transmission routes, features of the infectious process), the population, movement patterns, and the environment. The article also addresses the need for validation of agent-based models. The reader's attention is drawn to the following important features of agent-based simulation models: the ability to model various scenarios on different scales (global, national, regional); the ability to use them in epidemiological studies when controlled experiments are impossible (e.g., consequences of non-compliance with preventive measures, spread of «cultural pathogens»); agents can make different decisions depending on their characteristics; consideration of behavioral aspects at the individual level; the ability to account for individual mobility and social contacts of agents. Agent-based simulation models are also well-suited for epidemiological modeling, particularly in the field of infectious disease surveillance, including emerging infections (e.g., COVID-19).

120-129 128
Abstract

Despite the high informativeness of minimally invasive methods for assessing respiratory system, lung tissue biopsy is often required to verify the diagnosis. Conventional methods include surgical biopsy, which considered as the gold standard but is associated with significant complications and mortality, and transbronchial biopsy, a less invasive but substantially less informative method. The most informative and novel approach is endobronchial ultrasoundguided transbronchial fine needle aspiration (EBUS-TBNA), which significantly surpasses forceps biopsy. Here I focus on EBUS-TBNA, highlighting its capabilities, the future prospects, expedient technical solutions in certain of its modification and the lack thereof in others, and approaches for the standardization.

130-139 204
Abstract

Adenomyosis, an ingrowth of endometrial tissue into the uterine wall, is a benign gynecological disease associated with infertility, pelvic pain, and abnormal uterine bleeding, having serious consequences for a woman's health and quality of life. Diagnosis of adenomyosis is often challenging due to the concomitant endometrial hyperplasia. The pathogenesis of adenomyosis has not yet been fully evaluated and requires further fundamental and clinical research. Here we analyze an impact of local and systemic immunity on the development and progression of adenomyosis. Several studies highlight the role of immune cell activation and excessive release of both proinflammatory and anti-inflammatory cytokines. Women with adenomyosis exhibit an imbalance in the interferon system, elevated levels of certain growth factors, defensins, and chemokines. Immune system disorders well correlate with the clinical symptoms of adenomyosis and entail adverse consequences for the female reproductive system. Oxidative stress that occurs in adenomyosis leads to an excess of free radicals that can damage the embryo. Alterations in cell adhesion levels prevent implantation, and morphological changes in the myometrium lead to a violation of its peristalsis and impede the sperm transport. Changes in the cytokine profile and the levels of transport proteins in women with adenomyosis may serve as predictors of the assisted reproductive technology outcomes. This review discusses the recent literature on adenomyosis and its impact on women reproductive function.



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ISSN 2500-0764 (Print)
ISSN 2542-0941 (Online)