[Modern Fixed Combinations in the Correction of Arterial Hypertension and Dyslipidemia].

Based on a clinical case report, the article shows the individual selection of effective therapy for a patient with arterial hypertension and dyslipidemia. Taking into account the risk factors for cardiovascular diseases, Equamer® was selected as a fixed combination of amlodipine + lisinopril + rosuvastatin capsules 10 mg+20 mg+10 mg (Gedeon Richter Plc, Budapest, Hungary). In the patient with hypertension, ischemic heart disease was verified, and stenting of the anterior descending artery was performed. According to the clinical guidelines, when arterial hypertension is associated with ischemic heart disease, the drug therapy of choice should be a combination of dihydropyridine slow calcium channel blockers with an angiotensin-converting enzyme inhibitor. The fixed triple combination of amlodipine, lisinopril, and rosuvastatin is one of the most appropriate in this clinical situation; this combination targets the two major risk factors for cardiovascular diseases, arterial hypertension and dyslipidemia.

Zero-waste preparation of mixed oxides for submicromolar sensing of Bentazone pesticide.

Necessity of having simple selective and robust methods for the analysis of environmentally relevant chemicals stimulates the development of new approaches to material preparation. Electrochemical sensing using electroactive substrates has proved efficient in the analysis of a wide range of pesticides and is widely used as a routine analytical method. Recently, mixed oxides showed promising electrocatalytic activity toward hazardous substrates. Prevalence of wet chemical methods in the synthesis of mixed oxides creates a methodological obstacle and inconvenience for their wide utilization. In this work we challenged the common preparation of mixed oxides with simple powder mixing and developed an electrode for bentazone detection with satisfactory detection limit (0.4 µM), recovery rate (≈104%), and a broad linearity range (1-45 µM). The proposed modified carbon paste electrode is highly selective and can be used for determination of bentazone in presence of interfering ions in water samples.

[Venous gangrene of small intestine following coronavirus infection (SARS-COVID-19)]. / Venoznaya gangrena tonkoi kishki na fone koronavirusnoi infektsii (SARS-COVID-19).

The pandemic of a new coronavirus infection has made certain adjustments to modern emergency medicine. Systemic endothelial dysfunction following COVID-19 largely determines hemostatic disorders. Numerous studies revealed that intense platelet adhesion followed by platelet aggregates in COVID-19 patients and functional disorders of fibrinolysis system are combined with activation and severe endothelial dysfunction. The last one inevitably leads to thrombosis and adverse vascular events. There are a lot of studies devoted to deep vein thrombosis and fatal massive pulmonary embolism under COVID-19 infection. However, there are no descriptions of mesenteric thrombosis followed by intestinal wall necrosis. Our experience is based on the treatment and follow-up of 14 patients with venous gangrene of small intestine under COVID-19-induced severe endothelial dysfunction. We present a 40-year-old man with coronavirus infection complicated by ileum gangrene and subsequent favorable outcome.

An extremely energetic cosmic ray observed by a surface detector array.

Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle's energy as [Formula: see text] (~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.

[Methylation of Regulatory Regions of DNA Repair Genes in Carotid Atherosclerosis].

The status of DNA methylation in the human genome changes during the pathogenesis of common diseases and acts as a predictor of life expectancy. Therefore, it is of interest to investigate the methylation level of regulatory regions of genes responsible for general biological processes that are potentially significant for the development of age-associated diseases. Among them there are genes encoding proteins of DNA repair system, which are characterized by pleiotropic effects. Here, results of the targeted methylation analysis of two regions of the human genome (the promoter of the MLH1 gene and the enhancer near the ATM gene) in different tissues of patients with carotid atherosclerosis are present. Analysis of the methylation profiles of studied genes in various tissues of the same individuals demonstrated marked differences between leukocytes and tissues of the vascular wall. Differences in methylation levels between normal and atherosclerotic tissues of the carotid arteries were revealed only for two studied CpG sites (chr11:108089866 and chr11:108090020, GRCh37/hg19 assembly) in the ATM gene. Based on this, we can assume the involvement of ATM in the development of atherosclerosis. "Overload" of the studied regions with transcription factor binding sites (according to ReMapp2022 data) indicate that the tissue-specific nature of methylation of the regulatory regions of the MLH1 and ATM may be associated with expression levels of these genes in a particular tissue. It has been shown that inter-individual differences in the methylation levels of CpG sites are associated with sufficiently distant nucleotide substitutions.

[Identification of Functionally Significant Polymorphic Variants in miRNA Genes in Carotid Atherosclerosis].

miRNAs are vital molecules of gene expression. They are involved in the pathogenesis of various common diseases, including atherosclerosis, its risk factors, and its complications. A detailed characterization of the spectrum of functionally significant polymorphisms of miRNA genes in patients with advanced carotid atherosclerosis is an important research task. We analyzed miRNA expression and exome sequencing data of carotid atherosclerotic plaques of male patients (n = 8, 66-71 years of age, 67-90% degree of carotid artery stenosis). For further study and analysis of the association between the rs2910164 polymorphism of the MIR146A gene and advanced carotid atherosclerosis, we recruited 112 patients and 72 relatively healthy Slavic residents of Western Siberia. A total of 321 and 97 single nucleotide variants (SNVs) were detected in the nucleotide sequences of pre- and mature miRNAs in carotid atherosclerotic plaques. These variants were located in 206 and 76 miRNA genes, respectively. Integration of the data of exome sequencing and miRNA expression revealed 24 SNVs of 18 miRNA genes that were processed to mature form in carotid atherosclerotic plaques. SNVs with the greatest potential functional significance for miRNA expression predicted in silico were rs2910164:C>G (MIR146A), rs2682818:A>C (MIR618), rs3746444:A>G (MIR499A), rs776722712:C>T (MIR186), rs199822597:G>A (MIR363). The expression of miR-618 was lower in carotid atherosclerotic plaques of patients with the AC rs2682818 genotype of the MIR618 gene compared with the CC genotype (log2FC = 4.8; p = 0.012). We also found an association of rs2910164:C (MIR146A) with the risk of advanced carotid atherosclerosis (OR = 2.35; 95% CI: 1.43-3.85; p = 0.001). Integrative analysis of polymorphisms in miRNA genes and miRNA expression is informative for identifying functionally significant polymorphisms in miRNA genes. The rs2682818:A>C (MIR618) is a candidate for regulating miRNA expression in carotid atherosclerotic plaques. The rs2910164:C (MIR146A) is associated with the risk of advanced carotid atherosclerosis.

[Preventive surgery after vascular reconstruction for chronic lower limb ischemia]. / Preventivnye khirurgicheskie vmeshatel'stva posle sosudistykh rekonstruktsii po povodu khronicheskoi ishemii nizhnikh konechnostei.

OBJECTIVE: To analyze the results of redo reconstructions of lower limb arteries in patients with obliterating atherosclerosis, immediate and long-term results in patients who underwent reconstructive interventions with occlusion of previous reconstruction and preventive interventions. MATERIAL AND METHODS: The study included 43 patients. The main group (group 1) consisted of 18 patients who underwent preventive vascular reconstructions. The control group enrolled 25 patients who underwent redo interventions for occlusion of previous reconstructions. The control group was divided into 2 parts; 15 patients had chronic limb ischemia (group 2), 10 patients had acute limb ischemia (group 3). Mean age of patients was 56.8±8.2 years; there were 37 (86%) men and 6 (14%) women. Multifocal vascular atherosclerosis was noted in 41 (95.3%) patients, carotid artery lesion - 29 (70.7%), coronary artery disease - 34 (79%). Patients with type II diabetes mellitus were excluded. RESULTS: We chose each surgical intervention considering preoperative diagnostic data. Open, endovascular and hybrid interventions were performed. There were no deaths and limb amputations in the 1st group. Two (13.3%) amputations were registered in the 2nd group, 3 (30%) amputations and 1 (10%) death were registered in the 3rd group. The follow-up period was 24 months. An 18-month freedom from amputations was 71.5%, 78% and 38%, respectively (p<0.05 compared to the 1st and 2nd groups). CONCLUSION: Preventive surgical interventions prevent ischemia and amputation, as well as improves the results of redo surgery.

Anisotropic acousto-optic interaction in a KRS-5 crystal.

We investigated the acoustic and acousto-optic parameters of cubic crystal KRS-5, which can be used in acousto-optic devices operating with optical radiation from visible to far infrared regions. The results of acoustic and acousto-optic property calculations are presented. Also, we present a possibility of obtaining optical birefringence in cubic material when external static pressure is applied to the KRS-5 crystal. We discuss in detail the results of anisotropic Bragg diffraction observation in cubic crystal in the presence of external static pressure.

[Lesions of the cortical part of the auditory analyzer in explosive injury]. / Narusheniya korkovogo otdela slukhovogo analizatora pri vzryvnoi travme.

A survey of 48 victims aged 19-36 years with explosive trauma and combined damage to the auditory system was conducted to assess the level of damage to nerve structures by analyzing the bioelectric activity of the cerebral cortex. All patients underwent electroencephalography (EEG). It is established that akubarotrauma of explosive genesis almost always leads to lesions of the function of the cortical part of the auditory analyzer. Desynchronized activity on the EEG after acubarotrauma is a favorable prognostic sign, indicating only functional disorders of the cortical part of the auditory analyzer. On the contrary, EEG changes of an organic type of cortical or stem nature are an unfavorable prognostic factor, usually accompanied by sensorineural hearing loss with prolonged and incomplete hearing recovery. Promising drugs for the treatment of otoneurological disorders are antihypoxants, in particular, derivatives of triazine indole, which affect the molecular mechanisms of hypoxia development.

Nonlocal Reaction-Diffusion Equations in Biomedical Applications.

Nonlocal reaction-diffusion equations describe various biological and biomedical applications. Their mathematical properties are essentially different in comparison with the local equations, and this difference can lead to important biological implications. This review will present the state of the art in the investigation of nonlocal reaction-diffusion models in biomedical applications. We will consider various models arising in mathematical immunology, neuroscience, cancer modelling, and we will discuss their mathematical properties, nonlinear dynamics, resulting spatiotemporal patterns and biological significance.

Zero Gravity is a Factor that Induces Negative Changes in Myelinated Fibers of the Spinal Tracts.

The development of hypogravitational motor syndrome is an essential negative consequence of weightlessness for humans; an important role in the pathogenesis of this syndrome is played by changes in axons of the spinal tracts. Myelinated fibers and transcriptome of the spinal cord were studied in mice exposed to hypogravity during a 30-day flight on a biosatellite. Morphometric analysis of myelinated fibers of the spinal tracts showed a decrease in the thickness of the myelin sheath. Analysis of spinal cord transcriptome revealed a decrease in the expression of genes involved in the myelination of nerve fibers. These results suggest that the processes of nerve fiber myelination are involved in the development of the hypogravitational motor syndrome under weightless conditions; the 7-day readaptation period was found to be insufficient for reversion of the negative changes in the myelinated fibers of the spinal cord.

Improving cancer treatments via dynamical biophysical models.

Despite significant advances in oncological research, cancer nowadays remains one of the main causes of mortality and morbidity worldwide. New treatment techniques, as a rule, have limited efficacy, target only a narrow range of oncological diseases, and have limited availability to the general public due their high cost. An important goal in oncology is thus the modification of the types of antitumor therapy and their combinations, that are already introduced into clinical practice, with the goal of increasing the overall treatment efficacy. One option to achieve this goal is optimization of the schedules of drugs administration or performing other medical actions. Several factors complicate such tasks: the adverse effects of treatments on healthy cell populations, which must be kept tolerable; the emergence of drug resistance due to the intrinsic plasticity of heterogeneous cancer cell populations; the interplay between different types of therapies administered simultaneously. Mathematical modeling, in which a tumor and its microenvironment are considered as a single complex system, can address this complexity and can indicate potentially effective protocols, that would require experimental verification. In this review, we consider classical methods, current trends and future prospects in the field of mathematical modeling of tumor growth and treatment. In particular, methods of treatment optimization are discussed with several examples of specific problems related to different types of treatment.

[Methods of decreasing the risk of repeat interventions in patients after arterial revascularization]. / Sposoby snizheniia riska povtornogo vmeshatel'stva u patsientov posle arterial'noi revaskuliarizatsii.

Discussed in the article are the main problems related to surgical treatment of patients with peripheral artery disease, particularly taking into consideration that in the world there are from 160 to 202 million people suffering from this disease, with two thirds of such patients having signs of lesions of coronary or cerebral arteries. Vascular reconstructive interventions cannot completely eliminate the problem, since in the postoperative period there may develop cardiovascular complications related to both the limb involved as either acute or progressing chronic ischaemia and arteries of other localization (coronary, cerebral). The risk of serious cardiovascular complications in patients with a history of endured adverse ischaemic events on the part of limbs is severalfold higher. To solve these problems and decrease complications, salicylic acid is used as basic therapy. Attempts at replacing it by another drug or combined therapy with an alternative antiaggregant showed no advantages in increased risk of massive haemorrhage. On the other hand, a combination of salicylic acid with an anticoagulant at a low dose, i. e., rivaroxaban 2.5 mg twice daily as compared with acetylsalicylic acid monotherapy made it possible to significantly decrease the incidence of various cardiovascular complications in the form of myocardial infarction, stroke, adverse ischaemic events on the part of the extremity, limb amputation.

[Hybrid interventions for acute thrombosis after reconstructive operations on lower-limb arteries]. / Gibridnye operatsii pri ostrykh trombozakh posle rekonstruktivnykh operatsii na arteriiakh.

BACKGROUND: A steadily growing number of primary lower extremity arterial reconstructions is inevitably followed by the need to perform repeat interventions. Shunt reocclusion may become a cause of return of ischaemia to the initial level, may significantly increase the degree of limb-threatening chronic ischaemia, as well as lead to the development of an acute condition requiring urgent corrective measures to be taken. A reoperation currently continues to remain the standard of treatment. Despite advances in modern resuscitation, the postoperative mortality rate in such patients reaches 20%. AIM: This study was aimed at assessing feasibility of hybrid technologies in acute thrombosis after reconstructive operations on lower-limb arteries. PATIENTS AND METHODS: We retrospectively analysed the results of treatment of 66 consecutive patients urgently admitted to the City Clinical Hospital named after S.S. Yudin from 2015 to 2020 with acute lower limb ischaemia caused by acute occlusion of the zone of primary vascular reconstructions previously performed at other medical facilities. Depending on the method of surgical treatment, the patients were divided into two groups. The Study group included 20 patients subjected to open surgical interventions followed by angiographic control and using one or other type of X-ray-endovascular treatment. Endovascular interventions were performed for more than 70% stenoses in the major arteries and zone of the previously performed operation. The Comparison group comprised 46 patients treated without endovascular technologies. They were subjected to thrombectomy from the vascular construction with/without reconstructive-restorative operations. RESULTS: Seventeen (85%) of the 20 Study group patients were operated on in a stagewise manner, with the first stage consisting of an open intervention - thrombectomy and reconstruction followed by angiographic control and roentgenendovascular treatment. The remaining three (15%) patients underwent simultaneous interventions. In the postoperative period, limb amputations were performed in ten (22%) Comparison group patients and in one (5%) Study group patient (p=0.049). There were three (7%) lethal outcomes in the Comparison group, with none in the Study group. CONCLUSION: A combination of open and endovascular interventions in patients with shunt occlusion after vascular reconstructions makes it possible to reveal the cause of shunt occlusion, as well as to remove multilevel lesions, minimizing surgical wound and contributing to reducing the amputation rate.

[Reperfusion syndrome: state of the art]. / Reperfuzionnyi sindrom. Sovremennoe sostoianie problemy.

Reperfusion syndrome is a complex series of clinical manifestations resulting from restoration of blood flow to previously ischaemic tissues. It is accompanied by damage to cells, tissues and organs at various levels, followed by the development of multiple organ failure. This review deals with the main pathophysiological mechanisms of the development of reperfusion syndrome in lesions of cardiac, cerebral and lower-limb vessels. Oxidative stress is considered to be the most important marker of ischaemia-reperfusion injury irrespective of the type of tissues affected. Presented herein are the data on contemporary possibilities of influencing various stages and components of the development of reperfusion injury by means of drug therapy, demonstrating that due to the importance of oxidative stress as a key link of reperfusion injury, antioxidant therapy should be the main component of prevention and treatment of reperfusion injury.

Possible Mechanisms of Axonal Transport Disturbances in Mouse Spinal Motoneurons Induced by Hypogravity.

The data obtained by transcriptome analysis of lumbar spinal cord segments, sciatic nerve, and the respiratory diaphragm of the mice performed after a space flight on board Bion-M1 biosatellite were processed by bioinformatic methods aimed at elucidation of the regularities in hypogravity-induced transcriptome changes in various compartments of motor neurons. The study revealed abnormalities of axonal transport in spinal motor neurons provoked by weightlessness. These data agree with the results of electron microscopy examination of the spinal cord in experimental animals. In space group mice sacrificed on the landing day, the content of perinuclear ribosomes in lumbar motoneurons surpassed that in control mice or in the recovery group examined 1 week after the flight. The data corroborate our hypothesis on contribution of axonal transport disturbances into pathogenesis of hypogravity motor syndrome. They can be employed as a launching pad for further study of hypogravity-triggered motor disorder mechanisms in order to elaborate the preventive therapy against the development of hypogravity motor syndrome in space flights.

[Endovascular revascularisation in patients with necrotic wounds and extended infrainguinal arterial disease]. / Endovaskulyarnaya revaskulyarizatsiya u patsientov s gnoino-nekroticheskimi ranami nizhnikh konechnostei s infraingvinal'nym protyazhennym porazheniem arterial'nogo rusla.

OBJECTIVE: To report own experience of endovascular interventions in patients with extended occlusive lesion (TASC II D) of the femoral-popliteal and tibial arteries and concomitant purulent-necrotic wounds. MATERIAL AND METHODS: We have analyzed literature data and own experience of endovascular interventions in patients with extended occlusive lesion (TASC II D) of the femoral-popliteal and tibial arteries and concomitant purulent-necrotic wounds. RESULTS: Endovascular strategy is preferable in a certain subgroup of patients with extended infrainguinal lesions. CONCLUSION: Considering own data, we assumed the need for routine correction of outflow pathways (simultaneous angioplasty of at least 2 tibial arteries). Primary results are encouraging, but further research is required.

[Current concepts of anticoagulant and antiplatelet therapy in patients with vascular pathology]. / Osnovnye pozitsii po antikoaguliantnoi i antiagregantnoi terapii u patsientov s patologiei sosudov na sovremennom étape.

The routine practice of a vascular surgeon is invariably associated with decreasing the risk of adverse cardiovascular events in patients presenting with either arterial or venous pathology. Antithrombotic therapy is one of the key approaches used to achieve this purpose. However, a wide variety of modern drugs inhibiting platelet aggregation and agents blocking the coagulation cascade, as well as their combinations makes the selection of the most appropriate treatment for a particular patient quite a difficult task. The choice should carefully be made taking into consideration the nosology, aetiology, accompanying diseases and therapy thereof, as well as the balance of the risk of ischaemic and haemorrhagic complications. Therefore, availability of modern antithrombotic drugs favourably contributing to a more personified approach to treatment is of utmost importance. Thus, for example, rivaroxaban, an anticoagulant belonging to the class of direct-acting oral factor Xa inhibitors, provides a possibility to select an optimal dosage and regimen for a particular patient with arterial or vascular pathology in practice of a cardiovascular surgeon.

[Additional possibilities in conservative treatment of patients with post-thrombotic disease of lower limbs]. / Dopolnitel'nye vozmozhnosti v konservativnom lechenii patsientov s posttromboticheskoi bolezn'iu nizhnikh konechnostei.

AIM: This study was undertaken to evaluate efficacy of Actovegin in the composition of comprehensive therapy in patients presenting with post-thrombotic disease of lower extremities free from trophic disorders. PATIENTS AND METHODS: The study included a total of 60 patients (28 men and 32 women) diagnosed as having post-thrombotic disease of lower limbs without trophic disorders (C1-C3 according to the CEAP classification), induced by previously endured iliofemoral phlebothrombosis. The duration of the disease varied from 1 year to 10 years. All patients for 10 days received Actovegin intravenously in drips at a dose of 1200 mg (30 ml of the drug reconstituted in 400 ml of normal saline) followed by continuing taking the drug orally in a daily dose of 1200 mg for 30 days. During the whole follow up period the patients wore class 2 compression stockings (RAL standard). The results of the carried out treatment in relation to the subjective complaints (pain, feeling of heaviness, convulsions, pruritus and paresthesias) were assessed by the visual analogue scale and based on the CIVIQ-20 questionnaire, with additionally measuring the malleolar circumference. RESULTS: On the background of the carried out therapy the patients demonstrated a significant decrease in the oedematous syndrome in the area of the ankles. This parameter decreased form 26.88±0.39 cm to 25.02±0.35 cm (p<0.05). The patients' complaints of tingling decreased form 5.73±0.79 to 2.32±0.68 points (p<0.05), the incidence and intensity of convulsions fell from 6.51±1.39 to 3.2±0.98 points (p<0.05). The intensity of the oedematous syndrome (swelling) decreased significantly from 8.11±1.75 to 4.33±1.20 points (p<0.05), the pain syndrome fell from 7.92±1.88 to 3.12±1.45 points (p<0.05), the feeling of heaviness in the lower limbs decreased from 8.52±1.73 to 3.91±1.48 points (p<0.05). Also, improvement of the general quality of life of patients was observed (the integral parameter decreased from 63.27±1.8 to 44.33±1.19 points, p<0.05).