[Diagnosis of benign laryngeal tumors using neural network]. / Diagnostika dobrokachestvennykh novoobrazovanii gortani s primeneniem neiroseti.

The article describes our experience in developing and training an artificial neural network based on artificial intelligence algorithms for recognizing the characteristic features of benign laryngeal tumors and variants of the norm of the larynx based on the analysis of laryngoscopy pictures obtained during the examination of patients. During the preparation of data for training the neural network, a dataset was collected, labeled and loaded, consisting of 1471 images of the larynx in digital formats (jpg, bmp). Next, the neural network was trained and tested in order to recognize images of the norm and neoplasms of the larynx. The developed and trained artificial neural network demonstrated an accuracy of 86% in recognizing of benign laryngeal tumors and variants of the norm of the larynx. The proposed technology can be further used in practical healthcare to control and improve the quality of diagnosis of laryngeal pathologies.

[The population morbidity with diseases of ear and mastoid and accessibility of otorhinolaryngological care].

The article analyses level and dynamics of morbidity of diseases of ear and mastoid in the Sakha Republic (Yakutia) in 2020-2021 and availability of otorhinolaryngological care. The methods of comparative statistics and mathematical analysis were applied to analyze official data provided by the Yakut Republic Medical Information and Analytical Center, the specialized Department of Otorhinolaryngology, the Republic Hospital № 2 - Center for Emergency Medical Care and the Federal State Statistics Service of Russia. The study established increasing trend of increasing morbidity of these diseases in both the adult and child population. In 2021, the growth rate of overall morbidity of adult population reached 17.7% and 8.8% in children, as compared to 2020. The primary morbidity of adults made up to 22.3%, in children - 15.7%. The comparative analysis demonstrated higher rates of general morbidity in the Republic: by 0.5% as compared with the Russian Federation and by 14.1% as compared with the Far Eastern Federal Okrug. The level of primary morbidity was lower than similar indicators of the compared territories by 17.1% and 3.0%, respectively. It is worth noting that analyzed morbidity of diseases of ear and mastoid reflects prevalence of ENT diseases in the region only indirectly, as the statistical data do not allow to estimate separately rate of upper respiratory tract lesions. Meanwhile, respiratory diseases rank first in the structure of population diseases in Yakutia. The growth of disability in children due to diseases of ear and mastoid requires attention. Among children of 0-17 years old, the indicator of primary disability increased from 0.38 to 0.8 per 10,000 of children population (increase of 110.5%); in children 0-3 years old - from 0.9 to 2.3 per 10,000 of the child population (an increase of 155.6%). The analysis of the number of beds in otorhinolaryngology wards established that that the bed capacity per 10,000 population was 0.6 that is significantly lower than the established standards. The article emphasizes need to adjust the Federal standards for hospital bed capacity, taking into account climatic and geographical conditions of the region, which contribute to spread and chronization of ENT diseases.

[Legal and forensic medical problems of postmortem donation]. / Pravovye i sudebno-meditsinskie problemy posmertnogo donorstva.

The article is devoted to legal and forensic medical problems of postmortem donation. The substantive provisions of postmortem donation, as well as normative legal documents regulating the processes of organs harvesting from deceased persons for subsequent transplantation and governing the work of transplantologists and forensic medical experts have been considered. The practical examples illustrating the essence and nature of the problem of postmortem forensic medical expertise of persons with absent organs has been given and the importance of the participation of a forensic medical expert involved in the decision-making process on possibility (or impossibility) of the corpse's organs and tissues explantation without prejudice to the further expert examination has been emphasized. The authors pay particular attention to the inadequacy of the legal framework, including the lack of a clear understanding of the legal status of the person holding the position of forensic medical expert, who provides an expert opinion on the organs' explantation.

Estimated Doses to the Heart, Lungs and Oesophagus and Risks From Typical UK Radiotherapy for Early Breast Cancer During 2015-2023.

PURPOSE: Breast cancer radiotherapy can increase the risks of heart disease, lung cancer and oesophageal cancer. At present, the best dosimetric predictors of these risks are mean doses to the whole heart, lungs and oesophagus, respectively. We aimed to estimate typical doses to these organs and resulting risks from UK breast cancer radiotherapy. METHODS: A systematic review and meta-analysis was conducted of planned or delivered mean doses to the whole heart, lungs or oesophagus from UK breast cancer radiotherapy in studies published during 2015-2023. Average mean doses were summarised for combinations of laterality and clinical targets. Heart disease and lung cancer mortality risks were then estimated using established models. RESULTS: For whole heart, thirteen studies reported 2893 doses. Average mean doses were higher in left than in right-sided radiotherapy and increased with extent of clinical targets. For left-sided radiotherapy, average mean heart doses were: 2.0 Gy (range 1.2-8.0 Gy) breast/chest wall, 2.7 Gy (range 0.6-5.6 Gy) breast/chest wall with either axilla or supraclavicular nodes and 2.9 Gy (range 1.3-4.7 Gy) breast/chest wall with nodes including internal mammary. For right-sided radiotherapy, average mean heart doses were: 1.0 Gy (range 0.3-1.0 Gy) breast/chest wall and 1.2 Gy (range 1.0-1.4 Gy) breast/chest wall with either axilla or supraclavicular nodes. There were no whole heart dose estimates from right internal mammary radiotherapy. For whole lung, six studies reported 2230 doses. Average mean lung doses increased with extent of targets irradiated: 2.6 Gy (range 1.4-3.0 Gy) breast/chest wall, 3.0 Gy (range 0.9-5.1 Gy) breast/chest wall with either axilla or supraclavicular nodes and 7.1 Gy (range 6.7-10.0 Gy) breast/chest wall with nodes including internal mammary. For whole oesophagus, two studies reported 76 doses. Average mean oesophagus doses increased with extent of targets irradiated: 1.4 Gy (range 1.0-2.0 Gy) breast/chest wall with either axilla or supraclavicular nodes and 5.8 Gy (range 1.9-10.0 Gy) breast/chest wall with nodes including internal mammary. CONCLUSIONS: The typical doses to these organs may be combined with dose-response relationships to estimate radiation risks. Estimated 30-year absolute lung cancer mortality risks from modern UK breast cancer radiotherapy for patients irradiated when aged 50 years were 2-6% for long-term continuing smokers, and <1% for non-smokers. Estimated 30-year mortality risks for heart disease were <1%.

[Comparative analysis of clinical and functional parameters in patients with stable stage II-III keratoconus after implantation of corneal segments and fitting of scleral rigid contact lenses]. / Sravnitel'nyi analiz kliniko-funktsional'nykh pokazatelei u patsientov so stabil'nym keratokonusom II­III stadii posle implantatsii rogovichnykh segmentov i podbora skleral'nykh zhestkikh kontaktnykh linz.

The modern treatment strategy for keratoconus (KC) involves sequential application of medical technologies aimed at stabilizing pathological changes in the cornea and restoring visual acuity. PURPOSE: This study compares the effect of implantation of intrastromal corneal ring segment (ICRS) and fitting of individual scleral rigid contact lenses (RCLs) on visual functions in patients with stage II-III KC after previously performed corneal collagen cross-linking. MATERIAL AND METHODS: The Helmholtz National Medical Research Center of Eye Diseases examined and treated 34 patients (69 eyes) aged 18 to 33 years with stage II-III KC. The study included patients who had previously undergone standard corneal collagen cross-linking. Depending on the type of optical correction, the patients were divided into two groups: patients in group 1 underwent ICRS implantation using a femtosecond laser; patients in group 2 were fitted with individual scleral RCLs. RESULTS: Improvement in clinical and functional parameters was observed in both groups. A higher clinical and functional result was achieved in group 2. CONCLUSION: For patients with stable stage II-III KC, it is advisable to recommend fitting of individual scleral RCLs for visual rehabilitation.

Persistent deciduous teeth: Association of prevalence with breed, breed size and body weight in pure-bred client-owned dogs in the United States.

Dogs use their teeth for a multitude of tasks and, as such, it is vital for their health and wellbeing that their oral health is maintained. Persistent deciduous teeth (PDT), those that fail to fall out at the appropriate time, are associated with malocclusion (misaligned bite), soft tissue trauma and increased risk of periodontal disease. The objective of the current study was to perform a retrospective analysis of veterinary medical data to understand the effect of dog breed size, dog breed and body weight on prevalence of PDT. Medical records collected from almost 3 million dogs visiting a chain of veterinary hospitals across the United States over a 5-year period showed an overall prevalence of 7% for PDT, the data represented 60 breeds with extra-small breeds (<6.5 kg) showing significantly higher prevalence (15%) than all other breed sizes (P < 0.001). Statistical modelling of extra-small, small and medium-small breed sizes showed that those on Wellness Plans or that had not received a dental prophylaxis for at least two years had significantly increased odds of PDT being detected (Odds ratio 2.72-3.2 and 2.17-3.36 respectively, P < 0.0001). Dogs with a below ideal body condition score had a decreased odds of PDT (Odds ratio 0.57-0.89, P < 0.0001) whereas those above ideal had an increased odds (Odds ratio 1.11-1.60, P < 0.0001). The findings from this extensive dataset highlight the importance of regular veterinarian examinations to identify and remove PDT, helping to avoid increasing the risk of associated issues such as periodontal disease and malocclusion.

[Investigation of oncolytic potential of vaccine strains of yellow fever and tick-borne encephalitis viruses against glioblastoma and pancreatic carcinoma cell lines].

INTRODUCTION: Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form. OBJECTIVE: To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses. MATERIALS AND METHODS: Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1. Viral strains: 17D yellow fever virus (YF), Sofjin tick-borne encephalitis virus (TBEV). Virus concentration were determined by plaque assay and quantitative PCR. Determination of cell sensitivity to viruses by MTT assay. RESULTS: 17D YF was effective only against pancreatic carcinoma tumor cells MIA Paca-2 and had a limited effect against PANC-1. In glioblastoma cell lines (LN229, GL6, T98G), virus had no oncolytic effect and the viral RNA concentration fell in the culture medium. Sofjin TBEV showed CPE50 against MIA Paca-2 and a very limited cytotoxic effect against PANC-1. However, it had no oncolytic effect against glioblastoma cell lines (LN229, T98G and GL6), although virus reproduction continued in these cultures. For the GL6 glioblastoma cell line, the viral RNA concentration at the level with the infection dose was determined within 13 days, despite medium replacement, while in the case of the LN229 cell line, the virus concentration increased from 1 × 109 to 1 × 1010 copies/ml. CONCLUSION: Tumor behavior in organism is more complex and is determined by different microenvironmental factors and immune status. In the future, it is advisable to continue studying the antitumor oncolytic and immunomodulatory effects of viral strains 17D YF and Sofjin TBEV using in vivo models.

Prevalence and prognosis of PIK3CA mutations in Bulgarian patients with metastatic breast cancer receiving endocrine therapy in first-line setting.

BACKGROUND AND AIMS: In approximately 40% of patients with HER2-negative/HR-positive breast cancer tumors, the PIK3CA gene is mutated. Despite this, clinical outcomes vary between studies in this cohort. We aimed to ascertain the prevalence of PIK3CA mutations in patients with metastatic HR+/HER2- breast in Bulgaria, as well the evaluation and comparison of progression free survival (PFS) between wild-type (WT) and mutation-positive groups in the real-world setting. METHODS: Three oncology centers in Bulgaria collected 250 tissue samples between 2016 and 2022 for this multicentric retrospective study. PIK3CA mutations were identified using Real-Time qPCR. The median follow-up period was 35 months. RESULTS: The mean age of the mutant cohort was 57.6 ± 11.6 years, compared to 56.5 ± 12.2 years for the WT cohort (p = .52). The percentage of patients with visceral metastasis was 58.8% (n = 147). Approximately 84.3% (n = 210) of the patients had reached postmenopause. 29.2% (n = 73) of the patients had PIK3CA mutations. The predominant mutation was present in exon 20, H1047R (46.5%). We found a significant correlation only between the presence of a mutation and the metastatic diseases at diagnosis (p = .002). As first-line therapy, 67.1% of patients received endocrine therapy (ET) plus cyclin dependent kinase (CDK4/6) inhibitor, while the remainder received ET alone. The median PFS of patients in the group with the mutation was 32 months (95%, CI: 22-40) compared to 24 months in the WT cohort ((95%, CI: 21-36) (p = .45)); HR = 0.86 (95%, CI: 0.5-1.3) (p = .46). We corroborated our conclusion using propensity matching score analysis, (36 months [95% CI: 20-40] vs. 26 months [95% CI: 21-38], [p = .69]). CONCLUSIONS: We found that the prevalence of PIK3CA mutations in our patients was comparable to what has been reported in other nations. Our results suggest that PIK3CA mutational status has no bearing to ET efficacy in first-line setting.

[Postgenomic and structural changes in the myocardia of Wistar rats fed a high-salt diet].

The relationship between dietary sodium, hypertension, and cardiovascular injury is far from clear. One of the important links in this process can be microRNAs that have the ability to modulate gene expression at the post-transcriptional level. However, their role in this process has not been fully studied. In addition, further studies require the identification of structural changes in the myocardium in conditions of long-term consumption of a high-salt diet. The aim of the study was to evaluate the expression levels of nuclear transcription factor κB (NFκB), microRNA (miRNA)-21 and structural changes in the myocardium during long-term consumption of a diet containing 8% (high) sodium chloride in Wistar rats. Material and methods. 20 Wistar rats with initial body weight 280.5±42.7 g were divided into two equal groups. The high salt (HS) group received 8% NaCl in the diet, the control (NS) group received the standard diet (0.34% NaCl). After 4 months, systolic blood pressure was measured in rats using the cuff method on the tail; the myocardial mass index was assessed after dissection; histological and electron microscopic examination of the myocardium was performed, and the expression levels of miRNA-21 and NFκB in the myocardium were determined. Results and discussion. Consumption of a diet high in sodium chloride for 4 months did not significantly affect the level of systolic blood pressure in normotensive Wistar rats, but led to an increase in myocardial mass index by 25.0% (p<0.05). In the HS group, hypertrophy of cardiomyocytes and an increase in the wall thickness of arterial vessels were revealed. The area of perivascular fibrosis in rats of the HS-group was almost 1.8 fold higher than in the NS-group. In animals of HS-group, the relative levels of expression of NFκB (more than 2 times) and miRNA-21 (almost 6 times) increased compared with the control. It can be assumed that the negative impact on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and miRNA-21 activation. Conclusion. In Wistar rats, long-term use of a high-salt diet results in myocardial remodeling that is not associated with changes in blood pressure. At the same time, the adverse effects of high salt intake on the myocardium are mediated, in particular, by postgenomic mechanisms, namely an increase in the expression levels of NFκB and microRNA-21.

The Influence of Adiponectin on Transport of Low-Density Lipoproteins through Human Endothelial Cell Monolayer In Vitro.

The influence of adiponectin, a protein secreted by adipocytes, on the activation of transendothelial LDL transport, the initial event of atherogenesis, was studied. The addition of adiponectin to the cultured endothelial hybridoma EA.hy926 cells did not affect both basal and TNF-stimulated transendothelial transport of LDL. In addition, adiponectin affects neither expression levels of CAV1, SCARB1, and ACVRL1 genes encoding proteins involved in transendothelial LDL transport, nor the MMP secretion by the EA.hy926cells. At the same time, adiponectin suppressed the TNF-stimulated IL-8 production and expression of the adhesion molecule gene ICAM1 in these cells. Thus, adiponectin reduces proinflammatory activation of EA.hy926 cells, which is not accompanied by changes in the transendothelial LDL transport. We speculate that anti-inflammatory action of adiponectin is the base for the influence of this adipokine on atherogenesis.

[The relationship between the relative length of leukocyte telomeres and mtDNA copy number and acute coronary syndrome in a 15-year follow-up.]

OBJECTIVE: to study the association of relative leukocyte DNA telomere length with death from natural causes during a 15-year follow-up in a middle-aged and elderly Siberian population. Study of the association of the relative length of leukocyte telomeres (LTL) with fatal outcomes during a 15-year follow-up of a random population sample formed in 2003-2005 (n=9 360, 45-69 years old, Novosibirsk, HAPIEE project). The main group included the persons died from natural causes (except external) without a previous history of CVD and cancer (n=609); controls were stratified by sex and age (n=799). The analysis of relative LTL at baseline was performed using quantitative real-time PCR. We estimated the odds ratio of all-cause death per 1 decile shortening of LTD as a continuous variable in a multivariable-adjusted logistic regression. The carriers of shorter telomere carriers had an increased risk of death from natural causes over the next 15 years (OR=1,37, 95% CI 1,31-1,44) per decile of LTL decrease, regardless of other factors. The risk coefficients were similar for death from CVD (1,39), cancer (1,42), and other non-external causes (1,51). In studied middle-aged and elderly Siberian (Caucasoid) population cohort the LTL was an independent inverse predictor of the 15-year risk of death from natural causes.