[Modern possibilities for transcatheter pulmonary valve replacement]. / Sovremennye vozmozhnosti transkateternogo protezirovaniya klapana legochnoi arterii.

The literature review is devoted to transcatheter pulmonary valve replacement. The authors summarize the indications, clinical data and current capabilities of transcatheter pulmonary valve replacement. The authors also overviewed modern valves for transcatheter pulmonary artery replacement. Effectiveness of transcatheter pulmonary valve implantation has been substantiated. Various studies comparing the outcomes of different valve systems for endovascular implantation were analyzed. The authors concluded the prospects for transcatheter pulmonary valve implantation.

[Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia]. / Effektivnost' i bezopasnost' primeneniya etilmetilgidroksipiridina suktsinata u patsientov s khronicheskoi ishemiei golovnogo mozga.

Chronic cerebral ischemia (CCI) is a common cerebrovascular syndrome, the development of which is associated with a high risk of increasing cognitive, behavioral, and motor disorders, and the formation of a patient's dependence on others. Timely start of treatment can slow down the course of the disease, make it more favorable. The review considers the possibility of using the domestic neuroprotector mexidol in patients with CCI. The results of a series of clinical studies on the use of ethylmethylhydroxypyridine succinate (mexidol) in patients with CCI are analyzed. The effectiveness of the drug in relieving cognitive, affective and motor disorders is noted. Information about the good tolerance of mexidol is presented.

[Study of the influence of etoxidol on expression of follistatin-like protein-1 (FSTL-1) in myocardium after experimental infarction in rats]. / Issledovanie vliianiia étoksidola na ékspressiiu follistatin-podobnogo belka-1 (FSTL-1) v miokarde posle éksperimental'nogo infarkta.

In heart attack, FSTL-1 is actively secreted by cardiomyocytes, accelerates growth of heart myofibrils and stimulates of vascular endothelial growth factor expression. The aim of this work was to investigate the effect of Etoxidol on synthesis of FSTL-1 in rats after myocardial infarction. The experiments were performed on Wistar rats weighing 250-350 g with simulated myocardial infarction or intact (group 5). Animals of control groups (groups 1, 2) were treated with saline for 7 and 14 days; Ethoxidol (24 mg/kg) was injected to animals of experimental groups (group 3, 4) (the daily dose was 6.36 mg/animal) for 6 or 14 days. The injection volume was 0.2 ml. At the beginning and at the end of the study plasma concentrations of FSTL-1 were determined by the ELISA method. Myocardial FSTL-1 gene expression was determined by real-time PCR. At the end of the experiments, the hearts were also used for histochemical analysis. To determine the size of the scar formed after the modeled heart attack, we used the classic Mallory staining method. The results show that the development of experimental acute myocardial infarction is accompanied by a significant increase in FSTL-1 expression in the heart, which was detected on the 7th day and stored increased by 14 days after a heart attack. After therapy with Ethoxidol, a tendency to a decrease in the expression of FSTL-1 by the 14th day was observed; it coincided with the dynamics of the plasma protein FSTL-1 level. It can be assumed that the downregulation trend in the FSTL-1 expression is associated with a more effective repair process after a heart attack, since FSTL-1 increases precisely in response to myocardial damage and decreases when the incentives for its expression from damaged heart tissue are reduced. Indirectly, this assumption is confirmed by the detected tendency to reduce the size of post-infarction fibrosis in the treatment with Ethoxidol. The results indicate the ability of Ethoxidol to influence FSTL-1 synthesis of in rats after myocardial infarction.

[The efficacy of ethylmethylhydroxypyridine in the rehabilitation treatment of poststroke patients]. / Effektivnost' primeneniya etilmetilgidroksipiridina suktsinata v vosstanovitel'nom lechenii patsientov, perenesshikh ishemicheskii insul't.

The analysis of the clinical efficacy and safety of ethylmethylhydroxypyridine succinate (mexidol) in the complex of rehabilitation measures in patients after ischemic stroke (IS) shows that course treatment with mexidol improves the recovery of neurological functions, decreases neurological deficit, cognitive disorders, including memory impairment, and manifestations of asthenic syndrome, increases the level of social adaptation and improves the psycho-emotional state of patients, reduces spasticity, increases motor and speech activity, praxis, reliably eliminates the ignoring syndrome. There is a decrease in the level of total cholesterol and low-density b-lipoproteins in the blood, and decrease in the severity of hypercoagulation. The results of the studies have convincingly shown the efficacy of mexidol at all stages of rehabilitation treatment of patients with IS.

105Pd NMR and NQR study of the cubic heavy fermion system Ce3Pd20Si6.

We report 105Pd nuclear magnetic resonance (NMR) and nuclear quadrupolar resonance (NQR) measurements on a single crystal of Ce3Pd20Si6, where antiferroquadrupolar and antiferromagnetic orders develop at low temperature. From the analysis of NQR and NMR spectra, we have determined the electric field gradient (EFG) tensors and the anisotropic Knight shift (K) components for both inequivalent Pd sites-Pd(32f) and Pd(48h). The observed EFG values are in excellent agreement with our state-of-the-art density functional theory calculations. The principal values of the quadrupolar coupling are [Formula: see text] MHz and [Formula: see text] MHz, for the Pd(32f) and Pd(48h) sites, respectively, which is large compared to the Larmor frequency defined by the gyromagnetic constant [Formula: see text] MHz/T for 105Pd. Therefore, the complete knowledge of K and the EFG tensors is crucial to establish the correspondence between NMR spectra and crystallographic sites, which is needed for a complete analysis of the magnetic structure, static spin susceptibility, and the spin-lattice relaxation rate data and a better understanding of the groundstate of Ce3Pd20Si6.

[Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with ischemic stroke]. / Effektivnost' i bezopasnost' primeneniya etilmetilgidroksipiridina suktsinata u patsientov s ostrym ishemicheskim insul'tom.

Stroke is still the most significant problem of the modern medicine and the leading cause of mortality and morbidity. There is the great experience of neuroprotection in patients with stroke in the Russian Federation. In clinical practice it's important to follow conditions, where neuroprotection will have maximum safety and effectiveness. The clinical trials of ethylmethylhydroxypyridine succinate (mexidol) in patients with acute ischemic stroke are described in the present review. Early management (in the first 6 hours) with mexidol significantly improve recovery dynamic and stroke outcome. Therapy with mexidol increases neurological recovery, improves vital activity and quality of life of patients with stroke. Furthermore, mexidol demonstrates high safety profile.

The Mechanism of Action of Ethoxidol on Oxidative Stress Indices in Heart Failure and Hypotension.

The aim of the investigation was to study the effect of 2-ethyl-6-methyl-3-hydroxypyridine malate (Ethoxidol) on the concentration of oxidative stress metabolites in patients with chronic heart failure (CHF) and hypertension. MATERIALS AND METHODS: 126 patients with FC I-III CHF have been examined. In addition to their individual therapy these patients received intravenous infusions of Ethoxidol. Blood content of 2,3-diphosphoglycerate (2,3-DPG), oxygen tension (рО2), pH, concentration of total peroxides, lactate, and aldosterone were identified. 2,3-DPG levels (g/L erythrocytes) in whole blood samples were determined by an enzyme assay using the reagent kit (Rosh, Germany), values of рО2, рСО2, рН, lactate in the venous blood were measured using gas analyzer Stat Profil pHOx Ultra (Nova Biomedical, USA). Indices of oxidative stress, i.e. the concentration of plasma total peroxides, were investigated by ELISA using OxyStat kit (Biomedica, Austria). Peripheral venous blood samples were collected from all patients before and 6 days after the daily intravenous Ethoxidol infusion. RESULTS: In patients with FC I, II, III CHF, on day 7 after intravenous Ethoxidol infusion at a dose of 100 mg/day, statistically significant growth (p=0.0002) of PaO2 level by 15.7, 17.4, and 22.8%, respectively, was noted. In patients with FC I, II, III CHF in the group receiving standard therapy, statistically significant (p=0.002) reduction of 2,3-DPG level by 2.7, 2.4, and 4.0%, respectively, was registered. On day 7 after the infusion of Ethoxidol at a dose of 100 mg/day, its decrease by 5.7, 10.5, and 26.2%, respectively (p<0.0001), was also observed. CONCLUSION: The increased concentrations of active oxygen forms have been established to negatively affect various bodily functions and adversely influence the pathophysiology of numerous diseases. Application of antioxidants, including Ethoxidol presented by us in this article, may become a clue to the development of preventive measures for many serious diseases.

Kondo-like phonon scattering in thermoelectric clathrates.

Crystalline solids are generally known as excellent heat conductors, amorphous materials or glasses as thermal insulators. It has thus come as a surprise that certain crystal structures defy this paradigm. A prominent example are type-I clathrates and other materials with guest-host structures. They sustain low-energy Einstein-like modes in their phonon spectra, but are also prone to various types of disorder and phonon-electron scattering and thus the mechanism responsible for their ultralow thermal conductivities has remained elusive. Our thermodynamic and transport measurements on various clathrate single crystal series and their comparison with ab initio simulations reveal an all phononic Kondo effect as origin. This insight devises design strategies to further suppress the thermal conductivity of clathrates and other related materials classes, with relevance for thermoelectric waste heat recovery and, more generally, phononic applications. It may also trigger theoretical work on strong correlation effects in phonon systems.

[Carboxytherapy - an innovative trend in resort medicine]. / Karboksiterapiia - odno iz innovatsionnykh napravlenii v kurortologii.

Carboxytherapy (the treatment based on carbon dioxide injections) is a multipurpose and widely used medical technology. The use of CO2 injections (intracutaneous, subcutaneous, and pneumopuncture) have substantially supplemented and increased the practical relevance of carboxytherapy as a method for the treatment of many diseases. Thanks to it physiological properties, CO2 has antihypoxic, antioxidant, vasodilatory, anti-inflammatory, analgesic, and spasmolytic activities; moreover, it improves blood viscosity, stimulates neoangiogenesis, and regenerative processes. Carbon dioxide is a sort of biochemical 'peacemaker' in tissue oxygenation: when blood cells are exposed to high CO2 concentrations (Bohr effect), the rate of gas exchange (CO2 and O2) increases. The human organism interprets carboxytherapy (local hypercapnia) as oxygen deficiency and responses to it by boosting not only the blood flow, but also the vascular endothelial growth factor which stimulates neoangiogenesis and in the long run improves blood supply and tissue trophism. The multiple mechanisms of action, polymodal efficacy, a tool kit with a wide range of detectors and various modes of treatment make carboxytherapy a popular medical technology all over the world, namely in cosmetology, dermatology, aesthetic medicine, angiology, orthopaedics, cardiology, neurology, pulmonology, gynaecology, urology, proctology, plastic and general surgery, and other areas. Carboxytherapy provides a perfect example of the off-label usage in medicine that made it one of the most extensively applied medical technology for the treatment of various diseases despite the lack of the preclinical data and scarce relevant information available in textbooks, reference books and booklets.

[Novel Possibilities in Pharmacotherapy of Patients With Chronic Heart Failure].

In this article we have described clinical pharmacology and data of clinical studies of an innovational drug valsartan + sacubitril in patients with chronic heart failure (CHF). The use of supramolecular complex valsartan + sacubitril allows to elevate quality of life and improve prognosis of patients with CHF. High efficacy of valsartan+sacubitril relative to impact on composite primary end-point (cardiovascular death + hospitalization due to CHF) was demonstrated in the clinical trial PARADIGM-HF in which it was compared with angiotensin converting enzyme inhibitor enalapril. Advantages of the use of valsartan + sacubitril for the budget were demonstrated in pharmacoeconomic studies. These advantages are maximally realized at long-term administration. Cost-efficacy of the use of valsartan+sacubitril in pharmacotherapy of CHF is comparable with that of statins in the treatment of ischemic heart disease or implantation of a cardioverter-defibrillator in prevention of sudden cardiac death. Thus, introduction of the drug into practice can be expected to reduce budget expenditures.

[Robot-assisted atrial septal defect closure in adults: first experience in Russia]. / Robot-assistirovannoe zakrytie defekta mezhpredserdnoi peregorodki u vzroslykh: pervyi opyt v Rossii.

AIM: To analyze immediate results of minimally invasive robot-assisted atrial septal defect (ASD) closure in adults. MATERIAL AND METHODS: For the period from March 2012 to November 2016 sixty patients with contraindications to endovascular procedure have undergone robot-assisted atrial septal defect closure at Meshalkin Siberian Federal Biomedical Research Center. Mean age was 34.5±11.3 years, body mass index - 24.6±4.0 kg/m2. 48 (80%) patients had NYHA class II before surgery. In 37 (61.7%) patients isolated ASD with deficiency or absence of one edge was diagnosed, isolated ASD with primary septum aneurysm - in 16 (26.7%) cases, 7 (11.6%) patients had reticulate ASD. 5 (8.3%) patients had concomitant tricuspid valve insufficiency required surgical repair (suture annuloplasty). All operations were performed under cardiopulmonary bypass with peripheral cannulation. Right-sided anterolateral mini-thoracotomy was used in the first 43 patients. Following 17 patients underwent completely endoscopic procedure. Depending on the shape, size and anatomical features of the defect we performed suturing (14 patients, 23.3%) or repair with xenopericardial patch (46%, 76.6%). RESULTS: Mean CPB and aortic cross-clamping time was 89.1±28.7 and 24.8±9.5 min, respectively. Postoperative variables: mechanical ventilation 3.3±1.5 hours, ICU-stay - 18.2±3.7 hours, postoperative hospital-stay - 13.4±5.7 days. There were no mortality and any life-threatening intra- and postoperative complications. Cases of conversion to thoraco-/sternotomy and postoperative bleeding followed by redo surgery were also absent. 23 patients were followed-up within 1 year, 6 patients - within 2 years, 3 patients - within 3 years. All patients were in NYHA class I-II with 100% freedom from ASD recanalization and redo surgery. According to echocardiography data there were decreased right heart, pulmonary artery pressure and preserved left ventricular function in early postoperative period and 1 year after surgery. CONCLUSION: In view of favorable course of postoperative period, no significant specific complications and encouraging immediate results we can talk about endoscopic robot-assisted ASD closure in adults as a safe and effective alternative to surgical treatment.

The Neutrons for Science Facility at SPIRAL-2.

The neutrons for science (NFS) facility is a component of SPIRAL-2, the new superconducting linear accelerator built at GANIL in Caen (France). The proton and deuteron beams delivered by the accelerator will allow producing intense neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono-kinetic energy spectra, respectively, will be available at NFS, produced by the interaction of a deuteron beam on a thick Be converter and by the 7Li(p,n) reaction on thin converter. The pulsed neutron beam, with a flux up to two orders of magnitude higher than those of other existing time-of-flight facilities, will open new opportunities of experiments in fundamental research as well as in nuclear data measurements. In addition to the neutron beam, irradiation stations for neutron-, proton- and deuteron-induced reactions will be available for cross-sections measurements and for the irradiation of electronic devices or biological cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful tool for physics, fundamental research as well as applications like the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors.

Kondo Insulator to Semimetal Transformation Tuned by Spin-Orbit Coupling.

Recent theoretical studies of topologically nontrivial electronic states in Kondo insulators have pointed to the importance of spin-orbit coupling (SOC) for stabilizing these states. However, systematic experimental studies that tune the SOC parameter λ_{SOC} in Kondo insulators remain elusive. The main reason is that variations of (chemical) pressure or doping strongly influence the Kondo coupling J_{K} and the chemical potential µ-both essential parameters determining the ground state of the material-and thus possible λ_{SOC} tuning effects have remained unnoticed. Here, we present the successful growth of the substitution series Ce_{3}Bi_{4}(Pt_{1-x}Pd_{x})_{3} (0≤x≤1) of the archetypal (noncentrosymmetric) Kondo insulator Ce_{3}Bi_{4}Pt_{3}. The Pt-Pd substitution is isostructural, isoelectronic, and isosize, and it therefore is likely to leave J_{K} and µ essentially unchanged. By contrast, the large mass difference between the 5d element Pt and the 4d element Pd leads to a large difference in λ_{SOC}, which thus is the dominating tuning parameter in the series. Surprisingly, with increasing x (decreasing λ_{SOC}), we observe a Kondo insulator to semimetal transition, demonstrating an unprecedented drastic influence of the SOC. The fully substituted end compound Ce_{3}Bi_{4}Pd_{3} shows thermodynamic signatures of a recently predicted Weyl-Kondo semimetal.

[PERSONALIZED MEDICINE IN INTERNAL MEDICINE].

Personalized medicine - a new direction in medicine, which is based on the study of various biomarkers and the use of new methods of molecular analysis (primarily evaluating the activity of isoenzymes of cytochrome P450), allowing individualized approach to the selection of both the drugs and the selection of the dosing regimen for the purpose of maximize the effectiveness and safety of pharmacotherapy. This personalized medicine is to change the development and use of preventive and curative interventions. Genetic polymorphism isozymes of cytochrome P450 may determine the individual activity of a particular isozyme, and thus, to predict the clinical effectiveness, and in some cases, the risk of adverse reactions. The article is an example of the use of information on the activity of cytochrome P450 in clinical practice in matters of diagnosis, treatment and prevention of diseases. The scheme of the five best-known activity of isoenzymes of cytochrome P450 is shown.

Outcomes of the Ross procedure in patients with an accompanying ascending aortic aneurysm.

Analysed in the article are the results of the Ross procedure in patients presenting with dilatation of the ascending portion of the aorta. A combination of aortic valve defects with dilatation of the ascending aorta of more than 45 mm supposes simultaneous prosthetic repair of the aortic valve and ascending aorta. The most common surgical procedure remains the Bentall-DeBono operation whose main disadvantage is associated with implantation of a mechanical prosthesis and the necessity of lifelong anticoagulant therapy. An alternative method is the Ross procedure demonstrating low risk of thromboembolic complications and freedom from anticoagulant therapy. Over the period from 2002 to April 2015, specialists of the Novosibirsk Scientific Research Institute of Circulatory Pathology named after Academician E.N. Meshalkin carried out a total of 162 Ross procedures in patients presenting with accompanying dilatation of the ascending aorta (more than 45 mm). The mean diameter of the aorta at the level of Valsalva sinuses amounted to 45.6±8.6 mm, with that of the ascending aortic portion equalling 53.4±7.8 mm. The technique of total replacement of the aortic root was used in all cases. When the aneurysm extended to distal portions of the ascending aorta, additionally performed were the following procedures: in 24 patients--reduction aortoplasty, in 6 patients--replacement of the resected aorta with an insert from xenopericardium, and in 2 patients with a vascular graft. The average duration of follow up amounted to 40.1±21.6 months. Ten patients were subjected to repeat operations for autograft dysfunction. There were no reoperations on the ascending portion of the aorta. The regression analysis revealed that predictors of the development of autograft dysfunction were the baseline dilatation of the fibrous ring (FR) of the aortic valve of more than 27 mm (p=0.04) and uncorrected arterial hypertension in the postoperative period (p=0.03). In the group of patients with the FR less than 27 mm there were no cases of allograft dysfunction. The results of the study suggest that the Ross procedure is a safe and effective method in patients with accompanying dilatation of the ascending aorta. Risk factors for autograft dysfunction are dilatation of the FR of the aortic valve exceeding 27 mm and arterial hypertension in the postoperative period.

[COMORBIDITY AND POLYMORBIDITY IN ADULTS AND CHILDREN IN THE LIGHT OF THE PROBLEM OF NSAID-GASTROPATHY].

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most demanded drugs. Paper presents the data review on the drug activity mechanisms, effectiveness, safety, and major drug interactions of NSAIDs at co-morbid conditions in different age groups, as well as measures of prevention of NSAID-gastropathy, which can occur even against the use of small doses of NSAIDs. The existing recommendations on the selection of NSAIDs and the complex therapy with drugs of this pharmacological group are shown in considering the individual characteristics of the patient, the pharmacological properties of drugs, the clinical picture of the disease, the presence of risk factors for adverse reactions and drug interactions.

[THE FEATURES OF SECRETION AND STOMACH MOTOR PROCESSES IN PATIENTS WITH DUODENAL ULCERS AS A CAUSE FOR REDUCING BIOAVAILABILITY OF PROTON PUMP INHIBITORS].

UNLABELLED: The article contains the modern data about the role of duodenal reflux in the development of acid-dependent diseases of stomach and duodenum. There are the results of studies in which the known quantitative parameters of duodenal reflux in the duodenal ulcer patients were simulated to identify their influence on the disintegration of enterosoluble dosage forms and the bioavailability of proton pump inhibitors (in healthy volunteers, patients with gasritis, exacerbation and remission of peptic ulcer disease the pharmacokinetics of lansoprazole, intragastric pH-metry with floating capsule for teleradio-pH-metry were investigated, and in an in vitro study the dissolution tests of proton pump inhibitors with pH 3 and pH = 4 were made). CONCLUSION: The high-amplitude oscillations of intragastric pH, observed during exacerbation of duodenal ulcer, can lead to an early disintegration of enteric-coated dosage form of proton pump inhibitors in the stomach, its destruction and decreased bioavailability.

Compact thermal neutron sensors for moderator-based neutron spectrometers.

In the framework of the NESCOFI@BTF project of the Italian Institute of Nuclear Physics, different types of active thermal neutron sensors were studied by coupling semiconductor devices with a suitable radiator. The objective was to develop a detector of small dimensions with a proper sensitivity to use at different positions in a novel moderating assembly for neutron spectrometry. This work discusses the experimental activity carried out in the framework of the ERINDA program (PAC 3/9 2012) to characterise the performance of a thermal neutron pulse detector based on (6)Li.

Thermopower enhancement by encapsulating cerium in clathrate cages.

The increasing worldwide energy consumption calls for the design of more efficient energy systems. Thermoelectrics could be used to convert waste heat back to useful electric energy if only more efficient materials were available. The ideal thermoelectric material combines high electrical conductivity and thermopower with low thermal conductivity. In this regard, the intermetallic type-I clathrates show promise with their exceedingly low lattice thermal conductivities. Here we report the successful incorporation of cerium as a guest atom into the clathrate crystal structure. In many simpler intermetallic compounds, this rare earth element is known to lead, through the Kondo interaction, to strong correlation phenomena including the occurrence of giant thermopowers at low temperatures. Indeed, we observe a 50% enhancement of the thermopower compared with a rare-earth-free reference material. Importantly, this enhancement occurs at high temperatures and we suggest that a rattling-enhanced Kondo interaction underlies this effect.