Cholelithiasis is a common surgical disorder creating a high burden of the healthcare system. The introduction of minimally invasive technologies justifies the shift towards hospital-replacing models, but the institutional aspects of their use in the metropolis are still poorly understood. The study aimed to assess the role of hospital-replacing technologies in organizing elective surgical care provision to patients with cholelithiasis based on the retrospective analysis data for the years 2016–2025. A retrospective observational study was conducted based on the aggregate data of the Moscow City Health Department. The dynamics and structure of elective cholecystectomy procedures, the development of the short-stay unit (SSU) network, length of hospital stay, and age distribution were analyzed. The number of laparoscopic cholecystectomy procedures increased by 48%, the number of open surgical interventions decreased by 93.4%. The SSU network expanded from 5 to 30 units, the share of surgery due to cholelithiasis performed at the SSU reached 40.2% relative to the year 2016. The SSU stay was associated with the 75.0% bed-day reduction (to one day) and the actual hospital stay reduction by more than 80.0% (to 16.2 ± 7.4 h) compared to the round-the-clock hospital (RCH). Age differences (the share of patients over the age of 70 was 13.3% in the SSU vs. 36.0% in the RCH) support selective routing of patients at lower risk to the SSU. Conclusions: SSU has become an important organizational instrument of elective surgery due cholelithiasis that has ensured a sharp patient treatment time reduction over the preceding 10 years.
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Pulmonary fibrosis is characterized by irreversible remodeling of the lung tissue, with limited treatment options. Selective vitamin D receptor (VDR) agonists are regarded as promising antifibrotic agents, but the dose dependence of their effects in pulmonary fibrosis has been little studied. The aim of the experimental study was to carry out a comparative analysis of the effects of two doses of paricalcitol in experimental aerosol bleomycin-induced pulmonary fibrosis. The experiment was performed on 60 Wistar rats: an intact group (n = 6), a control group with fibrosis modeling (n = 18), and two experimental subgroups with intraperitoneal administration of paricalcitol at doses of 0.1 μg/animal (EG-A; n = 18) and 0.5 μg/animal (EG-B; n = 18) once every 3 days. The animals were withdrawn from the experiment on days 10, 20, and 30, with histopathological analysis and scoring on the modified Ashcroft scale, immunohistochemical study (CD68, CD80, CD163, MMP-9, TGF-β1, p38 MAPK, VDR), and analysis of the relative mRNA expression of IL1β, TNFα, TGF-β1, and SMA-α. Both doses of paricalcitol reduced the severity of the inflammatory and fibrotic changes, but the effect was dose-dependent: on day 30 the Ashcroft score was 5.01 ± 0.45 points in the control, 3.40 ± 0.28 in EG-A (–32.1%), and 2.12 ± 0.25 in EG-B (–57.7%; p < 0.05 compared with EG-A). Paricalcitol limited the early M1 response, reduced the number of CD163+ macrophages, and suppressed the expression of TGF-β1, MMP-9, and p38 MAPK. With the high dose, by day 30 the mRNA levels of IL1β, TNFα, TGF-β1, and SMA-α did not differ from those in the intact group. Thus, the antifibrotic action of paricalcitol is dose-dependent and is most pronounced at the later stages of the experiment.
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Bordetella bronchiseptica is a respiratory pathogen of humans and animals that infects a wide range of hosts. This study aimed to characterize the phylogenetic position and genomic features of 31 laboratory isolates of B. bronchiseptica, 25 of which were obtained from humans and six from animals. The studied isolates were compared with 30 reference genomes of B. bronchiseptica, B. pertussis, and B. parapertussis. The analysis included the determination of average nucleotide identity (ANI), phylogenetic reconstruction based on 120 marker proteins and 42 ribosomal proteins, and the identification of virulence factors, potential antibiotic resistance genes, prophage regions, and antiphage defense systems. A subsample of 20 genomes has also been subjected to pangenomic and metabolic analyses. In the overall dataset, B. pertussis and B. parapertussis formed compact clades, whereas B. bronchiseptica isolates were distributed across several phylogenetic lineages. B. bronchiseptica lines differed in their repertoires of virulence factors, putative antibiotic-resistance determinants, prophages, and antiphage defense systems. In the subsample of 20 genomes, representatives of the classical Bordetella retained the main modules of central metabolism and a substantial proportion of the shared gene clusters. The resulting data demonstrate a pronounced phylogenetic and functional genomic heterogeneity of B. bronchiseptica.
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Peritoneal carcinomatosis in colorectal and gastric cancer is associated with the extremely poor prognosis and the limited standard therapy efficacy, which suggests the need to develop new targeted drugs. The study aimed to assess the long-term outcomes of the efficacy of the RAS-GTPase peptide inhibitor (“Ing-Ras”) intraperitoneally administered by the PIPAC method to patients with stage III–IV gastric and colorectal tumors. A total of 38 patients (21 with colorectal cancer (CRC), 17 with gastric cancer (GC), including with peritoneal carcinomatosis) were included in the prospective open-label nonrandomized multicenter phase I/IIa trial. The long-term outcomes were assessed after 30 months of follow-up. A significant increase in the overall survival parameters was reported for both disease entities: the one- and two-year overall survival was 95.24 and 80.95% for CRC (historical control: 65–85% and 50–65%), 76.47 and 47.06%, respectively, for GC vs. 40–60% and 20–30%; progression and recurrence rates decreased significantly. Thus, the use of “Ing-Ras” makes it possible to increase the survival rate and reduce the recurrence rate relative to the historical control, which justifies conducting phase III trials.
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Parkinson's disease (PD) is a progressive neurodegenerative disease, the key pathogenetic feature of which is considered to be the degeneration nigrostriatal dopaminergic neurons and the decrease in striatal dopamine (DA) levels. The study aimed to assess the dynamic changes in the levels of DA, serotonin, and their main metabolites in the striatum of C57BL/6 mice with the chronic toxic PD model induced by administration of multiple doses of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) combined with probenecid. The use of such modeling protocol enables simulation of the long-lasting neurochemical alterations similar to the slow progressive course of the disease in humans. Neurotransmitters and their metabolites were quantified by high-performance liquid chromatography with electrochemical detection. The study results demonstrate the decrease in the total DA metabolism in both axon terminals and the synaptic cleft during early neurodegeneration typical for PD. The most pronounced decrease in the levels of DA and its metabolite DOPAC was observed a week after the course of MPTP/ probenecid injections: it was 36% and 32% of the control level, respectively. It is noteworthy that the DA and DOPAC levels remained decreased throughout 3 months and were restored to the control level as late as 6 months after the end of the course of MPTP/probenecid injections. In general, the model presented makes it possible to extend the window of neurodegenerative alteration manifestation to 3 months. The data obtained once again demonstrate a complex pattern of the effects of neurodegenerative and compensatory processes occurring at the earliest stages of neurodegeneration in PD.
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The problem of finding new treatment methods fo r children with autism spectrum disorder (ASD) remains urgent. One of the ways to correct the manifestations of ASD is the Early Start Denver model (ESDM). This article describes a clinical case of a patient (a boy) with ASD. The child began an 8-month ESDM-based psycho-correctional intervention at the age of 4 years and 2 months. Each session lasted 50 minutes; they were held twice a week. One of the parents (the boy's mother) was an active participant in the sessions. Before and after the intervention, the child’s condition was assessed using the ADOS-2 and CARS scales, the E. E. Lyaxo speech development questionnaire, a measure of helping-behavior severity, and EEG. According to the supervising psychiatrist and his parents, the boy’s behavior has improved. Test results indicated a reduction in autism symptom severity (ADOS-2 score: 5 to 4; CARS score: 32 to 24), an increase in the percentage of correctly completed speech tasks from the Lyaxo questionnaire (46.5% to 54.0%), and increases in instrumental (2 to 10), emotional (0 to 5), and altruistic (0 to 9) helping behaviors, as well as in a combined altruistic–emotional helping behavior score (0 to 8). After the ESDM intervention, the child showed stronger µ-rhythm amplitude desynchronization on EEG during observation of another person’s actions. This clinical observation confirms that the ESDM technique can significantly impact the neural circuits underlying social behavior.
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The evolution of multi drug-resistant bacterial diseases enforces the need for new botanical anti-microbiological drugs. Curry leaf (Murraya koenigii L. Spreng) is often used in traditional medicine; however the pharmacognosic effects and extraction efficiency need to be affirmed meticulously. The study aimed at qualitative phytochemical profiling and physicochemical standardization of M. koenigii leaf powder by aqueous, ethanolic and methanolic solvent systems, conducted for the first time. MICs were measured by microdilution to determine antibacterial activities against a panel of clinically relevant pathogens; the disc diffusion method was used for microbiological analysis. Tukey's post-hoc test was used after one-way ANOVA to examine statistical differences. Physicochemical examination showed a total ash value of 15.4% ± 0.3% w/w and a low moisture content of 4.2% ± 0.3% w/w. We detected bioactive secondary metabolites, including as tannins, alkaloids, and, flavonoids were validated by phytochemical screening, with alcoholic solvents showing higher extraction yields than water. The ethanolic extract showed strong antibacterial activity against Proteus mirabilis (21.0 mm) and Staphylococcus aureus (21.0 mm) in disc diffusion experiments, but the aqueous extract was totally inactive (0.0, p < 0.001). Bacillus sp. and Streptococcus mutans showed the lowest MIC values for the ethanolic extract (0.156 mg/mL). These results validate M. koenigii's potential development as a natural therapeutic agent by establishing pharmacognostic quality markers for the plant and showing that its ethanolic extract contains extremely powerful antibacterial agents, especially effective against Gram-positive clinical isolates.
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The meniscus degeneration pathogenesis is important for understanding and developing new treatment methods; it includes biochemical, structural, and microcirculatory alterations affecting all joint structures. The study aimed to perform in vitro assessment of the effects of standard and photoactivated platelet-rich plasma (PRP) on the IL6, IL17A concentrations, expression of COL2A1 and CD95 apoptosis marker in human meniscus fibrochondrocytes in the IL1β-induced inflammation. The human knee meniscus cartilage tissue was collected from 12 somatically healthy donors aged 18 to 35 years for the experiment. Cells were divided into four groups: the first was intact (control), the second, third, and fourth ones were exposed to IL1β to induce degenerative alterations; the second one was supplemented with 0.9% NaCl, the third one with donor PRP, and the fourth one with photoactivated PRP. Parameters were determined after 48 h. Statistical analysis was performed in GraphPad Prism 9. The rm-ANOVA was used for related groups. Data were presented as mean ± SD, at p < 0.05. IL6 (79.6 ± 4.3 pg/mL vs. 28.4 ± 2.1 pg/mL), IL17A (42.8 ± 2.5 pg/mL vs. 14.2 ± 1.0 pg/mL), CD95 (28.5 ± 2.2% vs. 6.8 ± 0.7%) levels increased in group II compared to group I; COL2A1 levels decreased from 1.00 ± 0.08 to 0.42 ± 0.0). IL6 levels decreased to 55.1 ± 3.4 pg/mL, IL17A — to 29.4 ± 2.1 pg/mL, CD95 — to 17.2 ± 1.5%, and COL2A1 levels increased to 0.71 ± 0.06 in group III compared to group II. IL6 levels decreased to 38.2 ± 2.6 pg/mL, IL17A — to 18.6 ± 1.7 pg/mL, CD95 — to 9.4 ± 0.8%, and COL2A1 levels increased to 0.94 ± 0.07 (p < 0,05) in group IV compared to group III. Standard PRP has a positive effect on meniscus tissue in vitro after 48 h. The effect is enhanced after the PRP exposure to red light.
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