Background. Described more than half a century ago, the countercurrent multiplication mechanism in the loop of Henle remains hypothetical; it suggests that tubular flow is significantly influenced by physicochemical processes that have yet to be quantified. Objective: To develop a model of tubular fluid dynamics and establish a numerical criterion, where a decrease below unity (threshold value) indicates pathological flow deceleration (tubular stasis) in the loop of Henle, leading to subsequent metabolic stress on the epithelial cells.

Methods. The study used mathematical modeling to account for specific flow characteristics within nephron tubules; given the absence of smooth muscle, tubular fluid dynamics are driven primarily by osmotic (electrochemical) effects.

Results. The findings provide a means to quantify (numerically or computationally) the flow capacity of the loop of Henle. This issue has long attracted the attention of specialists, most of whom support the hypothetical countercurrent multiplication in the ascending limb. This mechanism assumes passive Na+ efflux from the tubular lumen to the interstitium to maintain the longitudinal osmotic gradient, which drives the tubular fluid dynamics.

Conclusion. The results suggest that various factors indirectly slowing the tubular fluid dynamics (such as lymphostasis and venous stasis) impede the passive Na+ efflux from the ascending limb. This triggers metabolic activation in the epithelial cells in this region, increasing the facultative production of adenosine triphosphate to drive active lumen-to-interstitium Na+ efflux. Chronic metabolic stress (catabolism) remodels mitochondrial biogenesis in the epithelial cells of the loop of Henle, creating conditions for the formation of calcium phosphate aggregates in the basal labyrinth.

Background. Alcohol remains the most commonly consumed psychoactive substance associated with cognitive impairment, which poses a significant public health concern. By damaging various regions of the brain, particularly the hippocampus, ethanol exposure causes serious neuropsychiatric disorders. In this connection, restoration of its structural integrity plays a key role in treating the consequences of chronic alcohol intoxication.

Objective. To study the pathomorphological changes in pyramidal neurons across different subfields of the rat hippocampus following chronic alcohol intoxication and treatment with new derivatives of neuroactive amino acids (glufimet and mefargin).

Methods. A preclinical randomized controlled trial was conducted on 28 ten-month-old outbred female Wistar rats weighing 280–320 g. The animals were divided into an intact group (Group I) and three experimental groups (II–IV). In Groups II–IV, chronic alcohol intoxication was induced by replacing drinking water with a 10 % (v/v) ethanol solution sweetened with sucrose (50 g/L) for 24 weeks. After that, they were administered 0.1 mL saline solution per 100 g of body weight (Group II/control), glufimet at a dose of 28.7 mg/kg (Group III), or mefargin at a dose of 25 mg/kg (Group IV). Qualitative signs of neuronal damage in the hippocampal pyramidal layer were assessed via microscopic detection of cytoplasmic chromatolysis, karyolysis, shrunken perikarya and nuclei, and nuclear hyperchromasia. Cellular and nuclear swelling, as well as the presence of hypocellular areas, were also evaluated. Morphometric analysis was performed using cross-sectional micrographs to determine the mean absolute areas of neuronal nuclei and perikarya, the relative area of all perikarya and neuropils per field of view, and the granular layer width. The proportion of shrunken and hyperchromic neurons was also calculated. Statistical analysis was conducted using the Statistica 12 software (StatSoft, USA). Differences were considered statistically significant at p < 0.05.

Results. Chronic alcohol intoxication led to a marked increase in the number of hyperchromic and chromatolytic shrunken neurons. This was accompanied by a neuronal loss in the hippocampal CA1–CA3 pyramidal layer, alongside the appearance of hypocellular areas and an increase in the number and size of glial cells and their nuclei. In Group III, glufimet improved cytoarchitecture in the hippocampal CA1–CA3 pyramidal layer relative to untreated female rats. Perikarya were predominantly round in shape and slightly enlarged, with no observable areas of cellular depletion. The absolute areas of perikarya and neuronal nuclei in all studied hippocampal subfields were statistically significantly greater than those in Group II — by an average of 31.3 % (p < 0.05) and 45.2 % (p < 0.05), respectively. The pyramidal layer width was comparable to that of intact animals. The proportion of shrunken neurons with hyperchromic nuclei was 42.1 % lower (p < 0.05), while the relative area of perikarya was 19.8 % (p < 0.05) greater compared to Group II. Mefargin, a γ-aminobutyric acid derivative administered to the female rats in Group IV, produced similar effects, albeit to a slightly lesser extent. Specifically, the pyramidal layer width was 12.9 % (p < 0.05) greater in the subfields CA1 and CA2, and the proportion of shrunken neurons with hyperchromic nuclei in the subfields CA1–CA3 was 11.1 % lower compared to the control group. The mean areas of neuronal perikarya and nuclei were greater by 54.9 % (p < 0.05) and 96.5 % (p < 0.05), respectively, than those in Group II, exceeding the values observed in intact animals.

Conclusion. Chronic alcohol intoxication leads to marked morphological changes in the rat hippocampal CA1–CA3 pyramidal neurons. Glufimet, a new glutamic acid derivative administered to animals following prolonged alcohol intoxication, helped to preserve the cytoarchitecture of the hippocampal CA1–CA3 pyramidal layer. These findings, together with data from previous studies, may serve as a basis for the development of a neuroprotective drug that can counteract the negative effects of alcohol on the central nervous system.

Background. The COVID-19 pandemic has revealed previously overlooked clinical features of infectious and inflammatory kidney diseases in pediatric patients. The SARS-CoV-2 virus was found to have a direct cytopathic effect on renal tissue, exacerbating pyelonephritis through the development of tubulointerstitial abnormalities and dysregulation of the immune response. In post-COVID-19 pediatric patients, pyelonephritis presents with more pronounced clinical and laboratory manifestations, often taking an atypical course, which hinders timely diagnosis and contributes to the progression of chronic kidney disease. In this connection, it is essential to identify sensitive diagnostic biomarkers and revise therapeutic strategies, taking the post-viral condition into account.

Objective: To assess the diagnostic value of biomarkers of tubuloglomerular dysfunction (γ-glutamyltransferase, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1) in children with post-COVID-19 acute pyelonephritis.

Methods. A cross-sectional observational study was conducted involving 63 children aged 9–12 years with clinically- and laboratory-confirmed acute pyelonephritis. The pediatric patients were divided into Group 1 (n = 34) and Group 2 (n = 29). The control group (Group 3) comprised 14 age-matched, apparently healthy children (9–12 years old, inclusive), resulting in a total of 77 participants. Clinical evaluation and treatment were conducted in the Nephrology Department of the Samarkand Regional Children’s Multidisciplinary Medical Center (Ministry of Health of the Republic of Uzbekistan). Laboratory and diagnostic procedures were performed at the clinical diagnostic laboratory of the above-mentioned center and the L. M. Isaev Research Institute of Microbiology, Virology, Infectious and Parasitic Diseases (Samarkand). The evaluation was conducted from January 2021 to December 2022. The participants were enrolled upon hospital admission, taking the presence or absence of a history of COVID-19 into account. In order to assess the extent of tubular injury, the urinary excretion of key biomarkers was analyzed: kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, β₂-microglobulin, and γ-glutamyltransferase. Statistical analysis of the data was performed using Excel (Microsoft Office 2016, USA) and StatPlus software (version 7, AnalystSoft Inc., USA).

Results. The study results revealed statistically significant increases in the urine concentrations of all studied biomarkers compared to the control group. In Group 1, γ-glutamyltransferase levels were 4.5 times higher than those of the control group; kidney injury molecule-1 levels, 3.9 times higher; the levels of neutrophil gelatinase-associated lipocalin, 25.7 times higher; β₂-microglobulin levels, 7.5 times higher. Group 2 also showed significant differences in these biomarkers, although the changes were less pronounced: the concentrations of γ-glutamyltransferase, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and β₂-microglobulin exceeded control values by 1.4, 1.9, 10.9, and 3.5 times, respectively. The marked increase in these biomarkers, especially neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, indicates proximal and distal tubular injury along with tubulointerstitial inflammation. The elevated levels of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 reflect active processes of cellular injury and inflammation in the renal tubules, which can probably be attributed to the cytopathic effect of SARS-CoV-2 on the epithelium of proximal tubules.

Conclusion. In order to monitor latent tubular dysfunction in post-COVID-19 pediatric patients, it is recommended to conduct a screening assessment of urinary biomarker levels: γ-glutamyltransferase, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and β₂-microglobulin. Assessing these concentrations enables the identification of early signs of tubulointerstitial injury, evaluation of pathological activity in renal tubules, and risk stratification for chronic pyelonephritis progression. These findings offer significant clinical utility, providing a basis for early diagnosis, longitudinal monitoring, and development of individualized treatment strategies for children with post-COVID renal dysfunction.

Background. Vulvovaginal atrophy is a chronic, progressive condition associated with estrogen deficiency. While involutional changes are well-documented, the relationship between the vaginal microbiota and the local immune response in vulvovaginal atrophy remains insufficiently explored.

Objective: To examine the relationship between the composition and metabolic activity of the vaginal microbiota and local immune gene expression profiles in patients with vulvovaginal atrophy.

Methods. This observational cross-sectional cohort study included 88 postmenopausal women with vulvovaginal atrophy, divided into two groups: symptomatic (n = 42) and asymptomatic (n = 46). The control group (Group 3) comprised 50 healthy, reproductive-age women. Vaginal discharge was evaluated via smear microscopy, pH measurement, and vaginal cytology. Additionally, the vaginal microbiome was analyzed using a real-time polymerase chain reaction (Femoflor 16). The ImmunoQuantex test system was used to evaluate cathelicidin LL-37 levels and quantitative mRNA expression of immune response genes: interleukin-1 beta, interleukin-10, interleukin-18, tumor necrosis factor alpha, toll-like receptor 4, GATA binding protein 3, cluster of differentiation 68, and beta-2 microglobulin. Data were processed using specialized software: Statistica 6 (StatSoft, USA) and Microsoft Excel 2010 (Microsoft, USA). Differences were considered statistically significant at a p-value of < 0.05.

Results. The symptomatic patients (Group 1) exhibited marked dysbiosis consistent with bacterial vaginosis: a critical reduction in lactobacilli (45.2 % vs. 100 % in the other groups) and extensive colonization by opportunistic anaerobic flora. This was accompanied by significant local immune activation, including increased expression of pro-inflammatory markers (interleukin-1 beta, toll-like receptor 4, and GATA binding protein 3), suppression of interleukin-10, a high inflammatory index (>95 %), and elevated LL-37 levels. A strong positive correlation was found between toll-like receptor 4 expression and total microbial load (r = 0.87). In Group 2 (“silent” vulvovaginal atrophy), the microbiota and immune profile did not differ from those of the control group, despite the presence of atrophy. Thus, the development of clinical symptoms in vulvovaginal atrophy is directly linked to the onset of severe dysbiosis, which triggers a potent pro-inflammatory cascade, rather than to the atrophy itself.

Conclusion. The development of clinical symptoms in vulvovaginal atrophy is associated not only with estrogen deficiency but also with the emergence of severe dysbiosis, which triggers a marked pro-inflammatory immune response. The “silent” form of vulvovaginal atrophy occurs without significant immune activation. A comprehensive diagnostic approach to vulvovaginal atrophy should include an assessment of the microbiota and local immune status to tailor patient management strategies.

Background. Abdominal surgical conditions are among the most prevalent in emergency surgery. The high frequency of concomitant diseases and the need to select the optimal treatment strategy underscore the importance of implementing simultaneous laparoscopic procedures, which can minimize surgical trauma and improve outcomes.

Objective. To evaluate the clinical efficacy and safety of simultaneous laparoscopic procedures in the treatment of concomitant abdominal surgical diseases.

Methods. A comparative, observational, non-randomized clinical study was conducted to evaluate the outcomes of 120 patients with calculous cholecystitis concomitant with other abdominal surgical diseases (physical status class I–III). Through exact matching by age and pathology, two groups were formed to be comparable in key anthropometric data and physical status according to the American Society of Anesthesiologists classification. The main group (n = 60) underwent simultaneous laparoscopic procedures performed according to an original algorithm using a precision dissection technique, while the control group underwent simultaneous open surgeries (n = 60). The study assessed intraoperative parameters, complication rates according to the Clavien–Dindo classification, autonomic regulation dynamics using the Index of Regulatory System Activity, and long-term quality of life (the 36-Item Short Form Health Survey, or SF-36) at 12 months. Statistical analysis was performed employing IBM SPSS Statistics 26.0 (IBM Corp., USA) and Microsoft Excel 2016 software (Microsoft, USA), with the use of Student’s t-test, Mann—Whitney U test, and Pearson’s chi-square test. A p-value of < 0.05 was considered statistically significant.

Results. The combination of laparoscopic procedures resulted in a 39.4% reduction in mean operative time (95.2 ± 12.5 vs. 157.1 ± 16.5 min in the open surgery group; p = 0.011) and a 2.2-fold decrease in blood loss (120 ± 30 vs. 260 ± 40 mL; p = 0.014). The overall complication rate in the main group was 4.1 times lower than in the control group (11.7% vs. 48.3%; p = 0.0001), while the risk of severe postoperative complications (Grade IIIb) decreased fourfold (5.0% vs. 20.0%; p = 0.012). Postoperative mortality was 0% in the laparoscopic group and 5.0% in the control group. By Day 7, the Index of Regulatory System Activity in the main group had normalized (3.4 ± 0.9 points), whereas functional stress persisted in the open surgery group (5.5 ± 0.7 points; p < 0.001). Length of hospital stay was 1.6 times shorter (6.4 vs. 10.2 days; p = 0.009). One year after simultaneous laparoscopic procedures, the SF-36 Physical Component Summary score improved by 41%, significantly exceeding the 24% improvement observed in the control group (p = 0.011).

Conclusion. Simultaneous laparoscopic procedures performed for concomitant abdominal diseases demonstrate high clinical efficacy and safety. This approach reduces the operative time, minimizes blood loss, lowers complication rates, and accelerates patient recovery. These findings support the widespread adoption of this method in abdominal surgery.

Background. The onset of atherosclerosis is often associated with the development of atherogenic changes in lipid and carbohydrate metabolism, which may manifest as metabolic syndrome, visceral obesity, endothelial dysfunction, and nonalcoholic fatty liver disease. It is of interest to study the association of 25(OH)D deficiency with cardiometabolic risk factors, as well as its impact on the development of metabolic and immunological changes.

Objective. To study the features and prevalence of atherogenic risk factors in adolescents with fatty liver disease and different blood 25(OH)D levels.

Methods. An observational cross-sectional study was conducted involving 120 adolescents aged 12–17 years (Tanner stages II–V) with ultrasound-detected nonalcoholic fatty liver disease. The participants, all residents of Arkhangelsk, were observed at the outpatient diagnostic and consultation center of the Northern State Medical University (Ministry of Health of the Russian Federation). The primary objective was to assess metabolic and atherogenic abnormalities, along with potential atherogenic risk factors, in adolescents with nonalcoholic fatty liver disease and different blood 25(OH)D levels. The patients were divided into two groups according to the median 25(OH)D value (14.36 ng/mL) of the entire sample: Group 1 (n = 60) with levels below the median and Group 2 (n = 60) with levels above the median. Atherogenic abnormalities were assessed based on the levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total lipid peroxides, uric acid, glucose, insulin, and blood C-reactive protein concentration, as well as insulin resistance index. Statistical analysis was performed using STATA (version 12.0, StataCorp., USA), EpiInfo, and Epitable software. Differences were considered statistically significant at p < 0.05.

Results. Group 1 adolescents exhibited elevated median levels of uric acid, glucose, insulin, insulin resistance index, C-reactive protein, waist circumference, body mass index, and total lipid peroxides, as well as decreased levels of high-density lipoprotein cholesterol. These parameters differed from those observed in Group 2. The findings are supported by a high prevalence of atherogenic abnormalities among adolescents in Group 1: uric acid over 0.36 mmol/L; insulin resistance index over 2.7; glucose over 5.5 mmol/L; insulin over 10 µIU/mL; C-reactive protein over 5 mg/mL; lipid profile (low-density lipoprotein cholesterol over 3.34 mmol/L and triglycerides over 1.46 mmol/L). In both groups of adolescents with ultrasound-detected fatty liver disease, blood 25(OH)D level was negatively correlated with insulin resistance index, waist circumference, body mass index, total lipid peroxides, C-reactive protein, and uric acid.

Conclusion. The study confirmed an association between 25(OH)D level and atherogenic risk factors, chronic inflammation, and insulin resistance in adolescents with fatty liver disease.

Background. This study analyzes the structure and volume of workload among faculty members at Russian medical universities amidst growing student enrollment, as well as increasing requirements for clinical training, research productivity, and continuing professional development. The relevance of this study stems from the discrepancy between official standards and the actual excessive workload experienced by medical educators.

Objective: To provide empirical evidence of the workload structure and volume among medical educators within the regulatory requirements for higher education in Russia.

Methods. The study drew on data from a large-scale questionnaire survey of 346 medical educators from three universities of different status, as well as five expert interviews. A typology of faculty members was proposed: “clinical practitioners” (active work with patients), “theorists” (analytical and laboratory work), and “non-clinical specialists and nurses.” Data analysis methods included descriptive statistics, correlation of indicators, and comparison (between faculty members at medical and non-medical universities).

Results. Approximately 60% of faculty members combine academic roles with clinical practice. The heaviest workload is observed among “clinical practitioners,” who are more actively involved in teaching residents and graduate students and conducting continuing professional development courses and electives, while also holding additional positions outside the university. Compared to their colleagues at non-medical universities, medical faculty members exhibit lower levels of research activity and academic mobility, publishing primarily methodological works. High research performance is demonstrated by university professors, as well as by department chairs who lead and coordinate the research activities of their units. Research productivity (article count) was found to be positively correlated with the number of positions held outside the university and the number of courses taught by the faculty member. About 10–15% of clinical practitioners balance a heavy workload with high research output, expert roles, and teaching more than three disciplines. Work overload among medical educators poses risks of occupational burnout and a perfunctory approach to teaching practical skills to students. The authors also suggest that effort-minimization strategies in publication activity are a direct consequence of work overload combined with stringent institutional requirements.

Conclusion. The structure of workload among medical educators is considerably more complex and extensive than what is prescribed by official standards. In order to reduce the workload and improve efficiency, it is proposed to for differentiate career paths (educator, clinician, or researcher), streamline working conditions practicing physicians (including through non-monetary incentives), reduce teaching load, and improve methodological, material, and organizational support for research activities.