Polymorphism of Transforming Growth Factor TGFB and Its Receptors TGFBRI, TGFBRII, TGFBRIIII Genes in Western Siberia Patients with Open-Angle Glaucoma.

Polymorphism of genes of transforming growth factor TGFB and its receptors (TGFBRI, TGFBRII, and TGFBRIIII) in patients with primary open-angle glaucoma was analyzed. The frequency of the TGFBRII CC genotype in patients is increased relative to the control group (OR=6.10, p=0.0028). Heterozygosity in this polymorphic position is reduced (OR=0.18, p=0.0052). As the effects of TGF-ß is mediated through its receptors, we analyzed complex of polymorphic variants of the studied loci in the genome of patients. Two protective complexes consisting only of receptor genes were identified: TGFBRI TT:TGFBRII CG (OR=0.10, p=0.02) and TGFBRII CG:TGFBRIII CG (OR=0.09, p=0.01). The study showed an association of TGFBRII polymorphism with primary open-angle glaucoma and the need to study functionally related genes in the development of the disease, which should contribute to its early diagnosis and prevention.

[Non-invasive diagnosis of brain gliomas by histological type using neuroradiomics in standardized regions of interest: towards digital biopsy]. / Neinvazivnaya diagnostika gliom golovnogo mozga po gistologicheskomu tipu s pomoshch'yu neiroradiomiki v standartizirovannykh zonakh interesa: na puti k tsifrovoi biopsii.

The future of contemporary neuroimaging does not solely lie in novel image-capturing technologies, but also in better methods for extraction of useful information from these images. Scientists see great promise in radiomics, i.e. the methodology for analysis of multiple features in medical image. However, there are certain issues in this field impairing reproducibility of results. One such issue is no standards in establishing the regions of interest. OBJECTIVE: To introduce a standardized method for identification of regions of interest when analyzing MR images using radiomics; to test the hypothesis that this approach is effective for distinguishing different histological types of gliomas. MATERIAL AND METHODS: We analyzed preoperative MR data in 83 adults with various gliomas (WHO classification, 2016), i.e. oligodendroglioma, anaplastic oligodendroglioma, anaplastic astrocytoma, and glioblastoma. Radiomic features were computed for T1, T1-enhanced, T2 and T2-FLAIR modalities in four standardized volumetric regions of interest by 356 voxels (46.93 mm3): 1) contrast enhancement; 2) edema-infiltration; 3) area adjacent to edema-infiltration; 4) reference area in contralateral hemisphere. Subsequently, mathematical models were trained to classify MR-images of glioma depending on histological type and quantitative features. RESULTS: Mean accuracy of differential diagnosis of 4 histological types of gliomas in experiments with machine learning was 81.6%, mean accuracy of identification of tumor types - from 94.1% to 99.5%. The best results were obtained using support vector machines and random forest model. CONCLUSION: In a pilot study, the proposed standardization of regions of interest demonstrated high effectiveness for MR-based differential diagnosis of oligodendroglioma, anaplastic oligodendroglioma, anaplastic astrocytoma and glioblastoma. There are grounds for applying and improving this methodology in further studies.

Problems and prospects for finding new pharmacological agents among adenosine receptor agonists, antagonists, or their allosteric modulators for the treatment of cardiovascular diseases.

A1-adenosine receptors (A1AR) are widely distributed in the human body and mediate many different effects. They are abundantly present in the cardiovascular system, where they control angiogenesis, vascular tone, heart rate, and conduction. This makes the cardiovascular system A1AR an attractive target for the treatment of cardiovascular diseases (CVD). The review summarizes the literature data on the structure and functioning of A1AR, and analyzes their involvement in the formation of myocardial hypertrophy, ischemia-reperfusion damage, various types of heart rhythm disorders, chronic heart failure, and arterial hypertension. Special attention is paid to the role of some allosteric regulators of A1AR as potential agents for the CVD treatment.

[The burden of COVID-19 in a heterogeneous population of immunocompromised patients - realities of the postpandemic].

On July 3, 2023, an interdisciplinary Council of Experts "The burden of COVID-19 in a heterogeneous population of immunocompromised patients - post-pandemic realities" was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.

[Surgical treatment of epilepsy in children with focal cortical dysplasia in central gyri]. / Khirurgicheskoe lechenie epilepsii u detei s fokal'nymi kortikal'nymi displaziyami tsentral'nykh izvilin.

Focal cortical dysplasias are known to be the most frequent and furtive lesions leading to intractable epilepsy in children. Epilepsy surgery in central gyri, been effective in 60-70% of cases, is still significantly challenging due to the high risk of postoperative permanent neurological impairment. STUDY AIMS: Assessment of the outcome after epilepsy surgery in children with FCD in central lobules. MATERIAL AND METHODS: Nine patients, median age 3.7 ys, IQR=5.7 ys (min 1.8- max 15.7 ys) with FCD in central gyri and DR-epilepsy underwent surgery. Standard preoperative evaluation included MRI and video-EEG. Invasive recordings were used in 2 cases, coupled by fMRI in 2. An ECOG and neuronavigation, as well as stimulation and mapping of primary motor cortex were used routinely during the procedure. Gross total resection was achieved in 7 patients according to postoperative MRI. RESULTS AND CONCLUSIONS: Six patients with new or worsening of already existing hemiparesis recovered within a year after surgery. At the last FU (med 5 ys) favorable outcome (Engel class IA) has been achieved in 6 cases (66.7%), while two patients with persisting seizures reported seizing less frequently (Engel II-III). Three patients were able to discontinue AED-treatment and four children resumed development with improvement in cognition and behavior.

[MR-guided non-invasive typing of brain gliomas using machine learning]. / Pervye rezul'taty neinvazivnogo tipirovaniya gliom golovnogo mozga po dannym magnitno-rezonansnoi tomografii s pomoshch'yu mashinnogo obucheniya.

Gliomas are the most common neuroepithelial brain tumors. The modern classification of tumors of central nervous system and treatment approaches are based on tissue and molecular features of a particular neoplasm. Today, histological and molecular genetic typing of tumors can only be carried out through invasive procedures. In this regard, non-invasive preoperative diagnosis in neurooncology is appreclated. One of the perspective areas is artificial intelligence applied for neuroimaging to identify significant patterns associated with histological and molecular profiles of tumors and not obvlous for a specialist. OBJECTIVE: To evaluate diagnostic accuracy of deep learning methods for glioma typing according to the 2007 WHO classification based on preoperative magnetic resonance imaging (MRI) data. MATERIAL AND METHODS: The study included MR scans of patients with glial tumors undergoing neurosurgical treatment at the Burdenko National Medical Research Center for Neurosurgery. All patients underwent preoperative contrast-enhanced MRI. 2D and 3D MR scans were used for learning of artificial neural networks with two architectures (Resnest200e and DenseNet, respectively) in classifying tumors into 4 categories (WHO grades I-IV). Learning was provided on 80% of random examinations. Classification quality metrics were evaluated in other 20% of examinations (validation and test samples). RESULTS: Analysis included 707 contrast-enhanced T1 welghted images. 3D classification based on DenseNet model showed the best result in predicting WHO tumor grade (accuracy 83%, AUC 0.95). Other authors reported similar results for other methods. CONCLUSION: The first results of our study confirmed the fundamental possibility of grading axial contrast-enhanced T1 images according to the 2007 WHO classes using deep learning models.

Diverse mantle components with invariant oxygen isotopes in the 2021 Fagradalsfjall eruption, Iceland.

The basalts of the 2021 Fagradalsfjall eruption were the first erupted on the Reykjanes Peninsula in 781 years and offer a unique opportunity to determine the composition of the mantle underlying Iceland, in particular its oxygen isotope composition (δ18O values). The basalts show compositional variations in Zr/Y, Nb/Zr and Nb/Y values that span roughly half of the previously described range for Icelandic basaltic magmas and signal involvement of Icelandic plume (OIB) and Enriched Mid-Ocean Ridge Basalt (EMORB) in magma genesis. Here we show that Fagradalsfjall δ18O values are invariable (mean δ18O = 5.4 ± 0.3‰ 2 SD, N = 47) and indistinguishable from "normal" upper mantle, in contrast to significantly lower δ18O values reported for erupted materials elsewhere in Iceland (e.g., the 2014-2015 eruption at Holuhraun, Central Iceland). Thus, despite differing trace element characteristics, the melts that supplied the Fagradalsfjall eruption show no evidence for 18O-depleted mantle or interaction with low-δ18O crust and may therefore represent a useful mantle reference value in this part of the Icelandic plume system.

[«Burr hole¼ microsurgery for vestibular schwannoma]. / «Burr hole¼ mikrokhirurgiya vestibulyarnykh shvannom.

OBJECTIVE: To evaluate the efficacy and safety of minimally invasive «burr hole¼ microsurgery for vestibular schwannoma. MATERIAL AND METHODS: A retrospective analysis of postoperative outcomes in 50 consecutive patients with vestibular schwannoma was performed. All patients underwent burr hole microsurgery between 2016 and 2020. RESULTS: All patients satisfactorily tolerated surgical treatment. Total resection was carried out in 21 (42%) cases, almost total resection - in 21 (42%) patients (>95% of baseline volume). Subtotal resection was performed in 8 (16%) cases. Mean surgery time was 132 min (range 60-340). Postoperative deterioration of facial nerve function occurred in 20 (40%) patients. Severe dysfunction (House-Brackmann grade V-VI) was observed only in three patients. Other 17 patients had moderate dysfunction of the facial nerve (House-Brackmann grade III-IV). Useful hearing was preserved in 6 (50%) out of 12 patients with preoperative useful hearing. CONCLUSION: Minimally invasive burr hole microsurgery is an effective method for vestibular schwannoma. Moreover, the proposed technique reduces surgery time due to simpler craniotomy and wound closure.

3D pCASL-perfusion in preoperative assessment of brain gliomas in large cohort of patients.

The aim of the study was to evaluate the role of pseudocontinuous arterial spin labeling perfusion (pCASL-perfusion) in preoperative assessment of cerebral glioma grades. The study group consisted of 253 patients, aged 7-78 years with supratentorial gliomas (65 low-grade gliomas (LGG), 188 high-grade gliomas (HGG)). We used 3D pCASL-perfusion for each patient in order to calculate the tumor blood flow (TBF). We obtained maximal tumor blood flow (maxTBF) in small regions of interest (30 ± 10 mm2) and then normalized absolute maximum tumor blood flow (nTBF) to that of the contralateral normal-appearing white matter of the centrum semiovale. MaxTBF and nTBF values significantly differed between HGG and LGG groups (p < 0.001), as well as between patient groups separated by the grades (grade II vs. grade III) (p < 0.001). Moreover, we performed ROC-analysis which demonstrated high sensitivity and specificity in differentiating between HGG and LGG. We found significant differences for maxTBF and nTBF between grade III and IV gliomas, however, ROC-analysis showed low sensitivity and specificity. We did not observe a significant difference in TBF for astrocytomas and oligodendrogliomas. Our study demonstrates that 3D pCASL-perfusion as an effective diagnostic tool for preoperative differentiation of glioma grades.

[Lessons learnt from 101 hemispheric pediatric epilepsy surgeries part ii: pitfalls and complications]. / Uroki 101 gemisferotomii u detei s polusharnoi simptomaticheskoi epilepsiei. Chast' II: oslozhneniya i oshibki.

OBJECTIVE: To evaluate the spectrum of pitfalls and complications after hemisherotomy basing on a retrospective study of a large consecutive pediatric cohort of patients from a single institution. MATERIAL AND METHODS: One hundred and one patients (med. age - 43 months) with refractory seizures underwent hemispherotomy. Developmental pathology was the anatomical substrate of disorder in 42 patients. The infantile post-stroke scarring and gliosis was the origin of epilepsy in the majority of 43 cases with acquired etiology. The progressive pathology (RE, S-W and TS) was the etiology in the rest of children (16 cases). The lateral periinsular technique was used to isolate the sick hemisphere in 55 patients; the vertical parasagittal approach was employed in 46 cases. Median perioperative blood loss constituted 10.5 ml/kg, but was markedly larger in kids with hemimegaly (52.8 ml/kg); 57 patients needed hemotransfusion during surgery. Median length of stay in ICU was 14.7 hours, and the length of stay in the hospital until discharge - 6.5 days. Eight patients underwent second-look surgery to complete sectioning of undercut commissural fibers. FU is known in 91 patients (med. length - 1.5 years). RESULTS: Major surgical complications with serious hemorrhage and/or surgery induced life-threatening events developed in 7 patients (one of them has died on the 5th day post-surgery for the causes of brain edema and uncontrolled hyponatremia). Various early and late infectious complications were noted in 4 cases. Ten patients experienced new not anticipated but temporary neurological deficit. Nine patients needed shunting for the causes of hydrocephalus within several first months post-hemispherotomy. Early seizure onset was associated with probability of all complications in general (p=0.02), and developmental etiology - with intraoperative bleeding and hemorrhagic complications (p=0.03). CONCLUSION: Children with developmental etiology, particularly those with hemimegalencephaly, are most challengeable in terms of perioperative hemorrhage and serious complications. Patients with relapse or persisting seizures should be evaluated for the possibility of incomplete hemispheric isolation and have good chances to become SF by re-doing hemispherotomy.

[Surgical treatment of sternal osteomyelitis and sternomediastinitis following cardiac surgery]. / Khirurgicheskoe lechenie osteomielita grudiny i sternomediastinita vsledstvie kardiokhirurgicheskikh operatsii.

OBJECTIVE: To analyze the incidence of cardiac surgeries and postoperative sternal osteomyelitis/sternomediastinitis, as well as treatment outcomes in these patients. MATERIAL AND METHODS: We summarized 171 patients with postoperative sternal osteomyelitis and sternomediastinitis. RESULTS: Organization of the Khabarovsk center for cardiovascular surgery in the Far Eastern Federal District was followed by 7.9- and 24.9-fold increase of the number of cardiac surgeries and CABG in 2005-2019, respectively. As a result, the number of patients with sternal osteomyelitis and sternomediastinitis after cardiac surgery increased from 0.50±0.10 to 1.59±0.17 cases per 100.000 (t=3.01; p<0.01). CPB and aortic clamping time (t=3.97; p<0.01), as well as surgery time (t=2.4; p<0.05) were significant risk factors of early postoperative complications. Two-stage surgical treatment of postoperative sternal osteomyelitis and sternomediastinitis (removal of ligatures and foreign bodies, sternal curettage with removal of sequesters at the first stage; resection of sternum with chest wall repair at the second stage) reduced hospital-stay from 31.9±13.4 to 29.2±10.8 days.

The rs1800470 Polymorphism of the TGFB1 Gene Is Associated with Myocardial Fibrosis in Heart Transplant Recipients.

The transforming growth factor ß1 (TGFß1), whose level may depend on the polymorphism of the TGFB1 gene, is involved in the formation of myocardial fibrosis. Myocardial fibrosis in a cardiac allograft may lead to a heart's structural and functional remodeling and subsequent dysfunction. The frequency of occurrence of alleles and genotypes of the TGFB1 gene polymorphic regions rs1800469, rs1800470, and rs1800471 in heart transplant recipients and their association with graft myocardial fibrosis were analyzed. Carriers of the CC genotype (p = 0.023, OR = 0.12, 95% CI: 0.017-1.0), and more often the G allele of rs1800471 (p = 0.023, OR = 7.76, 95% CI: 1.0-60.20), were found among heart transplant recipients less frequently than among healthy individuals. In patients with ischemic heart disease (IHD), the GG genotype was less common (p = 0.035, OR = 2.68, 95% CI: 1.061-6.793), while the A allele of rs1800469 was found more frequently (p = 0.035, OR = 0.37 95% CI: 0.148-0.942) than in patients with dilated cardiomyopathy (DCM). In heart transplant recipients with the AA genotype of rs1800470, myocardial fibrosis, verified by endomyocardial biopsy, was detected more often than in carriers of the G allele (OR = 10.4, 95% CI: 1.152-94.538, p = 0.013). The revealed differences suggest a relationship between TGFB1 gene polymorphism and graft myocardial fibrosis. Studies on a larger group of patients would make it possible to characterize the influence of genetic factors on the formation of myocardial fibrosis in heart transplant recipients.

All-optical modulation and detection using a gain medium in a pulse shaper.

We demonstrate all-optical modulation and ultrafast detection using an on-resonance optical gain medium, combined with spectral splitting in a Fourier transform pulse shaper. Multiple spectral channels of one optical beam can be independently modulated in time by another beam, allowing high-rate modulation and multiplexing without requiring ultrafast response from the gain medium. For detection of sub-picosecond signals we demonstrate a method of ultrafast signal detection (temporal imaging with no spatial resolution) that utilizes the spatio-temporal tilt of an optical pulse in a pulse shaper. The proposed methods can find applications in optical information technology and ultrafast imaging.

[Surgical treatment of epilepsy in children with focal cortical dysplasia]. / Khirurgicheskoe lechenie epilepsii u detei s fokal'noi kortikal'noi displaziei.

OBJECTIVE: Surgery is the first-line treatment option in children with FCD and refractory epilepsy, but the rate of success and patient numbers who became free of seizures vary widely from series to series. STUDY AIMS: To elicit variables affecting the outcome and predicting achievement of the long-term seizure-free status. MATERIAL AND METHODS: One hundred sixty-nine children with cortical dysplasia and DR-epilepsy underwent surgery Preoperative evaluation included prolonged video-EEG and MRI (in all patients) and neuropsychological testing when possible. Fourteen patients underwent invasive EEG, fMRI and MEG were used also in some cases. Including 27 repeat procedures the list of overall 196 surgeries performed consists of: cortectomy (lesionectomy with or without adjacent epileptogenic cortices) ­ in 116 cases; lobectomy ­ in 46; and various disconnective procedures ­ in 34 patients. Almost routinely employed intraoperative ECOG (134 surgeries) was combined with stimulation and/or SSEP in 47 cases to map eloquent cortex (with CST-tracking in some). A new permanent and not anticipated neurological deficit developed post-surgery in 5 cases (2,5%). Patients were follow-upped using video-EEG and MRI and FU which lasts more than 2 years (median ­ 3 years) is known in 56 cases. Thirty-two children were free of seizures at the last check (57,2% rate of Engel IA). A list of variables regarding patients' demography, seizure type, lesion pathology and localization, and those related to surgery and its extent were evaluated to figure out anyone associated with favorable outcome. RESULTS: Both Type II FCDs and their anatomically complete excision are positive predictors for favorable outcome and achievement of SF-status (p<0,05). Residual epileptic activity on immediate post-resection ECOG do not affect the outcome. CONCLUSION: Patients with Type II FCD, particularly with Type IIb malformations are the best candidates for curative surgery, including cases with lesions in brain eloquent areas. Kids with Type I FCD have much less chances to become free of seizures when attempting focal cortectomy. However, some of them with early onset catastrophic epilepsies may benefit from larger surgeries using lobectomy or various disconnections.

Composition of Colon Microbiota in Rats Treated with ACTH(4-7)-PGP Peptide (Semax) under Conditions of Restraint Stress.

We studied the effect of Semax on the state of intestinal microbiota in rats subjected to restraint stress. Semax was injected to Wistar male rats intraperitoneally in doses of 5, 50, 150, 450 µg/kg 12-15 min before modelling chronic restraint stress. It was found that stress exposure reduced the number of obligate bacteria in the colon microbiota, but increased the content of opportunistic microorganisms. Semax in doses of 50 and 150 µg/kg prevented the stress-induced changes in the composition of colon microbiota. The observed effects of Semax might be mediated by the central neurotropic effects as well as by binding to peripheral melanocortin receptors of the intestine.

[CONSTITUTIONAL BASES OF ENSURING THE HUMAN RIGHT TO HEALTH: COMPARATIVE LEGAL ASPECT].

The objective of the article is to identify common and distinctive features of the constitutional provision of human right to health in Ukraine, the Czech Republic and the Republic of Poland on the basis of a comparative and legal study. The main task is to summarize the experience of the Czech Republic and the Republic of Poland, and taking it into account - to determine the directions of improving the constitutional legislation of Ukraine in this area. It has been established that the constitutional provision of human right to health in Ukraine is contained both in the Basic Law and in a number of constitutional and legal acts, and the conducted analysis of the relevant norms confirms the imperfection of the concepts and terms' definitions that should reflect the said right. The author has defined that the problems in the health care sector in Ukraine are: lack of a sustainable Concept of building a new national health care system, the slow pace of medical reform started only in 2017, and refusal from the Soviet centralized system of public health management. It has been found out that the Constitutions of Ukraine, the Republic of Poland and the Czech Republic have common features regarding the formulation of constitutional principles of ensuring human rights to health. At the same time, it has been found out that the experience of organizing the health care system in the Republic of Poland and the Czech Republic requires amendments to the constitutional and legal acts of Ukraine, which would aim at a clearer formulation of the definitions of the basic concepts and terms determining human right to health, the formation of decentralized health care system that would be in line with the basic principles of the EU policy in the health care sector.

State of Colon Microbiota in Rats during Chronic Restraint Stress and Selank Treatment.

We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 µg/kg 15 min before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.

[Treatment of patients with multiple trauma in multi-field hospital]. / Rezul'taty lecheniia bol'nykh s politravmoi v mnogoprofil'noi klinike.

AIM: To analyze treatment of victims with multiple trauma in multi-field hospital. MATERIAL AND METHODS: Retrospective analysis of 2139 medical records of patients with multiple trauma (NISS score over 17) was performed. In-hospital mortality, patient transfer time, dominant injury, hospital-stay, gender and age of victims were assessed. RESULTS: New diagnostic and treatment options allowed achieving significant decrease of mortality from 39.7% (2004) to 10.8% (2016). CONCLUSION: Improved mortality was achieved due to organized work of the 'regional traumatological systems'. Mortality rate was below 10.7% if victims were transferred to the hospital within 6 hours after trauma. The highest mortality was observed in patients who were transferred to the hospital within 6-12 hours after injury (20.3%).

Blood Serum Levels of Proinflammatory Cytokines (IL-1ß, IL-6, TNFα, IL-8, IL-12p70, and IFNγ) in Patients with Uterine Myoma.

We analyzed cytokine profile in blood serum of patients with uterine myoma and revealed significantly reduced level of IFNγ and a tendency towards a decrease in the levels of IL-1ß and TNFα; the levels of IL-6, IL-8, and IL-12p70 did not differ from those in healthy women. The drop in the concentrations of factors responsible for inflammation and angiogenesis in tissues are unfavorable for proliferation and differentiation of the uterine tissues.