Algorithm for Endovascular Treatment of Patients With Spinal Arteriovenous Malformations

Objective: To compare the endovascular treatment results in patients with spinal arteriovenous malformations (AVM) based on the proposed algorithm.   Materials and methods: We retrospectively analyzed the endovascular treatment results in 72 patients with various types of spinal AVMs for 2014-2021. We formed 2 main groups of patients based on the developed indications for neurophysiological monitoring and provocative tests (NFM and PT): group 1 (n = 63) was treated according to the algorithm, and group 2 (n = 9) was treated before the algorithm was implemented. Group 1 was divided into subgroup 1.1 (n = 42) including patients with no indications for NFM and PT and subgroup 1.2 (n = 21) with patients indicated for NFM and PT. Subgroup 1.2 was further divided into subsubgroup 1.2A (n = 2) with patients indicated for NFM and PT yet to be informative due to severe neurological deficit and subsubgroup 1.2B (n = 19) with patients that had indications for and successfully underwent NFM and PT. We compared patients between groups 1 and 2, subsubgroup 1.2B and group 2 to evaluate the effectiveness of the algorithm (radical nature of the treatment, functional status assessment, complications).   Results: Radical nature of spinal AVM treatment in group 1 was 79 % compared with 44 % in group 2 (P = 0.043). There was a significant improvement in motor function in group 1 compared with group 2 in each follow-up period (Р ≤ 0.007). Comparison of subsubgroup 1.2B and group 2 showed no significant differences (P = .05). The treatment led to complications in 5 patients (7 % of the total number of patients with spinal AVMs): 4 patients in group 2 and 1 patient in subsubgroup 1.2B. The effectiveness of the developed criteria was indirectly confirmed by difference in complications number between subsubgroup 1.2B and group 2 (P = 0.001).   Conclusions: Group 1 showed better treatment results, significant clinical improvement, high radical nature of treatment, and a low percentage of complications compared with group 2. The proposed algorithm proved effective for main tasks of endovascular treatment of spinal AVMs

DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes

Aims: Despite metformin being used as first-line pharmacological therapy for type 2 diabetes, its underlying mechanisms remain unclear. We aimed to determine whether metformin altered DNA methylation in newlydiagnosed individuals with type 2 diabetes. Methods and Results: We found that metformin therapy is associated with altered methylation of 26 sites in blood from Scandinavian discovery and replication cohorts (FDR < 0.05), using MethylationEPIC arrays. The majority (88%) of these 26 sites were hypermethylated in patients taking metformin for ~ 3 months compared to controls, who had diabetes but had not taken any diabetes medication. Two of these blood-based methylation markers mirrored the epigenetic pattern in muscle and adipose tissue (FDR < 0.05). Four type 2 diabetes-associated SNPs were annotated to genes with differential methylation between metformin cases and controls, e.g., GRB10, RPTOR, SLC22A18AS and TH2LCRR. Methylation correlated with expression in human islets for two of these genes. Three metformin-associated methylation sites (PKNOX2, WDTC1 and MICB) partially mediate effects of metformin on follow-up HbA1c levels. When combining methylation of these three sites into a score, which was used in a causal mediation analysis, methylation was suggested to mediate up to 32% of metformin’s effects on HbA1c. Conclusion: Metformin-associated alterations in DNA methylation partially mediates metformin’s antidiabetic effects on HbA1c in newly-diagnosed individuals with type 2 diabetes

Nephrostomy-free percutaneous nephrolithotripsy: intraoperative hemostasis methods of the percutaneous tract

Review based on the analysis of more than 40 scientific papers published in the Pubmed and Medline databases from 1984 to 2019, dedicated to intraoperative hemostasis of the percutaneous tract and its tightness during nephrostomyfree percutaneous nephrolithotomy (PCNL). The article aimed to summarize scientific data on this issue. We presented information about the history and development of percutaneous surgery in the treatment of urolithiasis. In our review, we have been demonstrated various methods of surgical and intraoperative hemostasis during nephrostomy-free PCNL

Interaction between some antibiotics and antioxidants

The study examined the interaction of antibiotics (gentamicin, ciprofloxacin, ceftazidime) and antioxidants (ascorbic acid, N-acetylcysteine, methylethylpyridinol) in vitro and in vivo. We conducted a dynamic study of the effect of antioxidants at concentrations of 0.5, 1, 2 and 4 mM on the activity of antibacterial agents in vitro for three strains of Klebsiella pneumoniae and three strains of Escherichia coli. The effect of antioxidants on the effectiveness of antibacterial therapy was studied in Wistar rats with experimental bacterial peritoniti

Abnormal epigenetic changes during differentiation of human skeletal muscle stem cells from obese subjects

Contains fulltext : 169731.pdf (publisher's version ) (Open Access)BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals. Functional follow-up experiments were performed using siRNA mediated gene silencing in primary human myoblasts and a transgenic mouse model. RESULTS: We observed genome-wide changes in DNA methylation and expression patterns during differentiation of primary human muscle stem cells (myoblasts). We identified epigenetic and transcriptional changes of myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6, PAX7, MEF2A, MEF2C, and MEF2D), cell cycle regulators, metabolic enzymes and genes previously not linked to myogenesis, including IL32, metallothioneins, and pregnancy-specific beta-1-glycoproteins. Functional studies demonstrated IL-32 as a novel target that regulates human myogenesis, insulin sensitivity and ATP levels in muscle cells. Furthermore, IL32 transgenic mice had reduced insulin response and muscle weight. Remarkably, approximately 3.7 times more methylation changes (147,161 versus 39,572) were observed during differentiation of myoblasts from obese versus non-obese subjects. In accordance, DNMT1 expression increased during myogenesis only in obese subjects. Interestingly, numerous genes implicated in metabolic diseases and epigenetic regulation showed differential methylation and expression during differentiation only in obese subjects. CONCLUSIONS: Our study identifies IL-32 as a novel myogenic regulator, provides a comprehensive map of the dynamic epigenome during differentiation of human muscle stem cells and reveals abnormal epigenetic changes in obesity

КОМПЛЕКСНОЕ ПРИМЕНЕНИЕ ЭНДОСКОПИЧЕСКИХ МЕТОДОВ В ДИАГНОСТИКЕ РАННИХ ФОРМ РАКА ТОЛСТОЙ КИШКИ

The aim of the research: explore the possibilities of modern visual differential diagnostics of early colon cancer and bening colon tumors.Methods.Results of endoscopic examination of 174 patients with unclear endoscopic data were analyzed. These patients underwent complex diagnostics, which revealed 293 tumors. Following groups were distinguished (according to the results of morphological study of biomaterial and visual endoscopic evaluation): early colon cancer – 28, lobular hyperplasia of the mucous shell – 38, polyps (adenomas with dysplasia varying degrees) – 184, limited infiltrative cancer – 37, neuroendocrine tumors – 6.Results.Visual and morphological data coincided in 89.3 % patients, sensitivity 93.9 %, specificity of 88.6 %, positive predictive value 90.4 %, negative predictive value 82.4 %, accuracy of 89.6 %.Conclusions. Use of the complex endoscopic diagnostics allows to identify the neoplastic changes of the mucous membrane in the early stages of development, and make a high-precision biopsy.Цель исследования: изучить возможности современной визуальной дифференциальной диагностики ранних форм рака и доброкачественных образований толстой кишки.Методы. В статье проанализированы результаты эндоскопического исследования 174 пациентов, у которых постановка диагноза вызывала затруднения. Этим больным было выполнено комплексное исследование, при котором выявлено 293 образования. Выделены следующие группы (по результатам морфологического исследования биоматериала и визуальной эндоскопической оценки): ранний рак толстой кишки – 28 образований, очаговая гиперплазия слизистой оболочки – 38, полипы (аденомы с дисплазией разной степени) – 184, ограниченный инфильтративный рак – 37, нейроэндокринные опухоли – 6.Результаты. Визуальные и морфологические данные совпали в 89,3 % случаев, чувствительность – в 93,9 %, специфичность в 88,6 %, прогностическая ценность положительного результата в 90,4 %, прогностическая ценность отрицательного результата в 82,4 %, диагностическая точность метода в 89,6 %.Выводы. Использование комплексной эндоскопической диагностики позволяет выявлять неопластические изменения слизистой оболочки на ранних стадиях развития, а также c высокой точностью производить забор биопсийного материала

FROM PERSONALIZED TO PRECISION MEDICINE

The need to maintain a high quality of life against a backdrop of its inevitably increasing duration is one of the main problems of modern health care. The concept of "right drug to the right patient at the right time", which at first was bearing the name "personalized", is currently unanimously approved by international scientific community as "precision medicine". Precision medicine takes all the individual characteristics into account: genes diversity, environment, lifestyles, and even bacterial microflora and also involves the use of the latest technological developments, which serves to ensure that each patient gets assistance fitting his state best. In the United States, Canada and France national precision medicine programs have already been submitted and implemented. The aim of this review is to describe the dynamic integration of precision medicine methods into routine medical practice and life of modern society. The new paradigm prospects description are complemented by figures, proving the already achieved success in the application of precise methods for example, the targeted therapy of cancer. All in all, the presence of real-life examples, proving the regularity of transition to a new paradigm, and a wide range  of technical and diagnostic capabilities available and constantly evolving make the all-round transition to precision medicine almost inevitable

КЛИНИЧЕСКИЙ ПРИМЕР: УСПЕШНОЕ ЛЕЧЕНИЕ СИНХРОННОГО РАКА ПРЯМОЙ И СИГМОВИДНОЙ КИШКИ С ПОМОЩЬЮ МИНИ-ИНВАЗИВНЫХ ТЕХНОЛОГИЙ

The case report describes successful treatment of synchronous low rectal and sigmoid cancers with mini-invasive technologies. Transanal endoscopic microsurgery allowed to perform sphincter-saving treatment. Treatment tactics for described tumor localizations are discussed. This case represents individualized approach to colorectal cancer patient, use of modern technologies in oncological surgery.В статье представлено клиническое наблюдение успешного лечения пациента с синхронно диагностированными первично-множественными опухолями толстой кишки, локализованными в нижнеампулярном отделе прямой кишки и в сигмовидной кишке, с помощью мини-инвазивных технологий. Применение трансанальной микрохирургии и лапароскопических технологий позволило выполнить сфинктеросохраняющее лечение данному пациенту. Дополнительно обсуждается выбор тактики лечения при подобной локализации опухолей. Представленное наблюдение является примером индивидуализации лечения и показывает ее важность в сочетании с современными технологиями в определении стратегии современной онкохирургии

Epigenome-Wide Association Study of Incident Type 2 Diabetes in a British Population: EPIC-Norfolk Study.

Epigenetic changes may contribute substantially to risks of diseases of aging. Previous studies reported seven methylation variable positions (MVPs) robustly associated with incident type 2 diabetes mellitus (T2DM). However, their causal roles in T2DM are unclear. In an incident T2DM case-cohort study nested within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort, we used whole blood DNA collected at baseline, up to 11 years before T2DM onset, to investigate the role of methylation in the etiology of T2DM. We identified 15 novel MVPs with robust associations with incident T2DM and robustly confirmed three MVPs identified previously (near to TXNIP, ABCG1, and SREBF1). All 18 MVPs showed directionally consistent associations with incident and prevalent T2DM in independent studies. Further conditional analyses suggested that the identified epigenetic signals appear related to T2DM via glucose and obesity-related pathways acting before the collection of baseline samples. We integrated genome-wide genetic data to identify methylation-associated quantitative trait loci robustly associated with 16 of the 18 MVPs and found one MVP, cg00574958 at CPT1A, with a possible direct causal role in T2DM. None of the implicated genes were previously highlighted by genetic association studies, suggesting that DNA methylation studies may reveal novel biological mechanisms involved in tissue responses to glycemia