Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing–Remitting from Secondary Progressive Multiple Sclerosis. A Review

Multiple sclerosis (MS) is a debilitating neurodegenerative, highly heterogeneous disease with a variable course. The most common MS subtype is relapsing–remitting (RR), having interchanging periods of worsening and relative stabilization. After a decade, in most RR patients, it alters into the secondary progressive (SP) phase, the most debilitating one with no clear remissions, leading to progressive disability deterioration. Among the greatest challenges for clinicians is understanding disease progression molecular mechanisms, since RR is mainly characterized by inflammatory processes, while in SP, the neurodegeneration prevails. This is especially important because distinguishing RR from the SP subtype early will enable faster implementation of appropriate treatment. Currently, the MS course is not well-correlated with the biomarkers routinely used in clinical practice. Despite many studies, there are still no reliable indicators correlating with the disease stage and its activity degree. Circulating microRNAs (miRNAs) may be considered valuable molecules for the MS diagnosis and, presumably, helpful in predicting disease subtype. MiRNA expression dysregulation is commonly observed in the MS course. Moreover, knowledge of diverse miRNA panel expression between RRMS and SPMS may allow for deterring disability progression through successful treatment. Therefore, in this review, we address the current state of research on differences in miRNA panel expression between the phases.

State-dependent inhibition of BK channels by the opioid agonist loperamide

Large-conductance Ca2+-activated K+ (BK) channels control a range of physiological functions, and their dysfunction is linked to human disease. We have found that the widely used drug loperamide (LOP) can inhibit activity of BK channels composed of either α-subunits (BKα channels) or α-subunits plus the auxiliary γ1-subunit (BKα/γ1 channels), and here we analyze the molecular mechanism of LOP action. LOP applied at the cytosolic side of the membrane rapidly and reversibly inhibited BK current, an effect that appeared as a decay in voltage-activated BK currents. The apparent affinity for LOP decreased with hyperpolarization in a manner consistent with LOP behaving as an inhibitor of open, activated channels. Increasing LOP concentration reduced the half-maximal activation voltage, consistent with relative stabilization of the LOP-inhibited open state. Single-channel recordings revealed that LOP did not reduce unitary BK channel current, but instead decreased BK channel open probability and mean open times. LOP elicited use-dependent inhibition, in which trains of brief depolarizing steps lead to accumulated reduction of BK current, whereas single brief depolarizing steps do not. The principal effects of LOP on BK channel gating are described by a mechanism in which LOP acts as a state-dependent pore blocker. Our results suggest that therapeutic doses of LOP may act in part by inhibiting K+ efflux through intestinal BK channels.

TRANSFORMATION OF FLOODPLAIN LANDSCAPES UNDER THE INFLUENCE OF NATURAL AND ANTHROPOGENIC CHANGES IN THE ENVIRONMENT (ON THE EXAMPLE OF THE ZAKHARKOVO FLOODPLAIN OF THE MOSCOW RIVER)

The Zakharkovskaya floodplain of the Moscow River is located directly above the Moscow Ring Road. It is an example of a natural structure that is spontaneously restored after long-term economic use (hayfields, pastures, long-term plowing, summer cottege settlements, drainage and irrigation channels, silt sites, etc.) under conditions of cessation of intensive anthropogenic impact. The article deals with the history of the formation and development of the Zakharkovskaya floodplain in prehistoric times (late Holocene), in the early historical period (beginning-middle of the second millennium AD), and in the late historical period-XIX-XXI centuries. The regulation of water flow, which has occurred in recent decades, is accompanied by a relative stabilization of the Moscow riverbed, turning it into a canal, reducing the intensity of channel deformations, leveling the bottom relief with its general deepening. As in other floodplain plots, the territory of floodplain leaves the flood zone; depressions are filled in, lakes are degraded, and man-made terrain is formed. At the same time, the current restrictions on access to the territory of the Zakharkovskaya floodplain for 10-15 years have created conditions for the restoration of natural structures, in particular, forest and shrub tracts, and increased the landscape and ecological attractiveness of floodplain lands.

Assessment of modern shoreline transformation rates on the banks of one of the largest reservoirs in the world (Kuibyshev reservoir, Russia) using instrumental methods

The study object is the Kuibyshev reservoir. The objective is to quantitatively assess reservoir bank landslides and shoreline abrasion in active zones based on the integrated use of modern instrumental methods. Different approaches are used to assess the intensity of landslide and abrasion processes: the specific volume and material loss index, the planar displacement of the bank scarp, and the planar-altitude analysis displacements of soil masses based on the analysis of slope profiles. Shoreline position for the past periods (1958, 1985, and 1987) was obtained from archival aerial photography data; data for 1975, 1993, 2010, 2011, and 2012 were obtained from high-resolution satellite image interpretation. Field surveys of these geomorphic processes at the study areas in 2002, 2003, 2005, 2006, 2014 were carried out using total stations; in 2012-2014 using terrestrial laser scanning and a UAV survey in 2019. The monitoring of landslide processes showed that the rate of volumetric changes at Site 1 remained rather stable during the measurement period with net material losses of 0.03-0.04 m3/m2/year. The most significant contribution to the average annual value of material loss was by snowmelt runoff. The landslide scarp retreat rate at Site 2 showed a steady decreasing trend, due to partial overgrowth of the landslide accumulation zone resulting in its relative stabilization. The average long-term landslide scarp retreat rate is 2.3 m/year. In recent years, landslide control measures realized at this site have reduced the landsliding intensity by more than 2.5 times to 0.84 m/year

The interrelation between the structural, electronic and energy parameters of nitrogen inversion in ammonia derivatives

The structural, electronic and energy parameters in the ground and transition states of inversion of the amines H2NXHn (XHn=CH3, NH2, OH, F, SiH3, PH2, SH, and Cl) have been calculated by using DFT (PBE96/def2-tzvpp) method. It was established that the increase of electronegativity of the substituents (the X atoms within the same period) leads to stabilization of the ground and transition states of the molecules. The increase in the inversion barriers is due to relative stabilization of the ground states, but not due to relative destabilization of the transition states. The inversion barriers rise with a decrease in conformational energies of the substituents, sums of valence angles at the nitrogen atoms, negative charges on them, energies of the nitrogen lone pairs and with an increase in s-character and population of the nitrogen lone pairs and difference between the energies of the nitrogen lone pairs in the ground and transition states. The main parameters that allow predicting the change of the nitrogen inversion barriers, independently of the type or volume of the XHn substituent, are s-character of the nitrogen lone pairs and difference between the energies of the nitrogen lone pairs. In all other cases, the correlations were found only for the amines containing the elements of the same period at the nitrogen atom. All structural and electronic parameters of amines containing the Х atoms from the second period are more sensitive to the changes of the ХНn substituents than the parameters of amines containing the Х atoms from the third period.

THE CHANGE OF GENERATIONS IN THE SOVIET REGIONAL ELITE (on the example of the Mordovian ASSR government in 1934–1991)

The article examines the development of the regional elite in the Soviet historical era using the example of the supreme state administration authority of a one particular autonomous republic. Several transformation stages in the elite of functionaries that was in power in Mordovia from the 1930s to 1991: 1) early 1930s – mid-1937 The national elite, formed during the Mordovian statehood formation, consisted, first, of autonomy supporters who were active in the 1920s; secondly, of people who came to the system of power as a result of Soviet «localization policy» applied to the control organs. They held leading positions until mass political repressions of 1937–1938.; 2) the end of the 1930s – the first half of the 1950s. There was an advancement of representatives of the so-called Stalinist control organs. Soviet «localization policy» was curtailed, and the number of the Moravians in the Soviet authorities decreased; the majority in the Council of People’s Commissars of the Mordovian ASSR was relatively young managers aged 30–40 years. Despite a frequent change of personnel, already in the second half of the 1940s there was a tendency of relative stabilization in the government composition; 3) mid-1950s – late 1960s. A core of experienced leaders who were working in their positions for quite a long time formed in the Council of Ministers. Its chairman I.P. Astaykin, who held this position for more than 15 years, had a great influence on the government; 4) the 1970s – late 1980s. After the change in the Republican party leadership, representatives of a new generation came to power. However, renewal of personnel was subsequently replaced by «stagnant» phenomena: a long stay in power of individual managers, gradual aging of the Council of Ministers members, the growth of the total number of managers; 5) late 1980s – 1991 As a result of the union center’s initiatives, as well as attainment of the maximum age by many regional leaders, there was some renewal in the composition of the Council of Ministers. But the old party and economic nomenclature continued to maintain its position in the republic until the very end of the Soviet system.

The formation and current state of the beaver population in the Kuznetskiy Alatau Mountains, South Siberia

The chronology of extinction and restoration of the Eurasian beaver population in the Kemerovo region is analyzed. The beavers exterminated at this territory at the end of the 18th century were reintroduced 60 years ago. The animals of Voronezh, Smolensk and Belarusian origin were used as the pedigree material. The stages of formation of the Castor fiber population through artificial and natural resettlement and the vectors of dispersion over the main rivers of the region are investigated. The first stage of formation of the Kuzbass population lasted more than 30 years, until 1995. There was the formation, enlargement and closure of isolated colonies into a meta-population. The animals actively settled and developed the most favorable habitats. The second period, which lasted almost 20 years, can be conveniently classified into three stages of rapid growth in numbers, which alternated with stages of relative stabilization. During this time, beavers settled in all large river basins, began to explore anthropogenic landscapes and began to appear near of human settlements. The assessment of the current spatial distribution of beavers in the conditions of the foothills of southern Siberia is made. On the model territory in the east of Kuzbass - the Kuznetskiy Alatau Nature Reserve and adjacent areas - the dynamics of the development of mountain streams by beavers in the absence and/or minimum hunting pressure is shown. Specialized protected area have played an important role in the formation of the modern Kuzbass beaver population. Now beavers have formed stable settlements even in the zone of subalpine meadows at altitudes up to 1350 m a. s. l. and migrate through mountain passes to the Krasnoyarsk Territory and the Republic of Khakassia. The current population of the Eurasian beavers in the Kuzbass exceeds 18,000 individuals, however, this important hunting resource is not exploited efficiently enough. If this trend persists, supported by the weak economic interest of trappers, the further development of the Kuzbass population of the Eurasian beaver will largely be determined by natural factors.

A Case Report of a Young Pregnant Woman with Preeclampsia and Acute Pulmonary Edema in Severe Transient Heart Failure

Introduction: Young pregnant woman (32 weeks) following one-month illnessesm, including peripheral edema, paresthesia and shortness of breath, for which no specific diagnosis was made in the evaluations; she was hospitalized with severe respiratory distress and pulmonary edema. Re-examination revealed severe systolic heart failure (left ventricular ejection fraction: 10-15%) with preeclampsia. After the relative stabilization of the patient's vital signs, the pregnancy was terminated. One week after termination of pregnancy, the patient's heart failure improved.

Extracorporeal Cardio-Pulmonary Resuscitation (E-CPR) in Traumatic Cardiac Arrests Caused by Penetrating Thoracic Injuries: A Series of Two Cases

Background. We present two cases of thoracic penetrating injuries that necessitated extracorporeal cardiopulmonary resuscitation (E-CPR). Patients.Two male patients were admitted to hospital within 20-25 minutes; one a chest stab wound and the other a gunshot injury. Upon ongoing CPR, patient #1 underwent resuscitative sternotomy. Bleeding from a right ventricle injury was controlled, but cardiac arrest (CA) re-occurred. Patient #2 underwent immediate surgery due to multiple rib fractures and massive hemopneumothorax, and experienced multiple CAs. Due to refractory asystole with ongoing CPR, ECMO was initiated after 100 and 135 minutes, respectively. Primary lactate level in case #1 and #2 was 8 and 20 mmol/L, respectively. Results. In both cases, femoral artery (17-19Fr) and vein (25-27Fr) were cannulated and connected to the Maquet ECMO circuit with a flow rate of 4-5 L/min. In both cases, ROSC was achieved within 20 minutes after ECMO initiation with relative stabilization of mean arterial pressure: 50-60 and >80 mmHg, respectively. In patient #1, postoperative bleeding necessitated re-thoracotomy and hemorrhage control. In patient #2, left pulmonectomy and ligation of intercostal arteries was performed. 12/30 units of red blood cells, 16/45 units of fresh frozen plasma, and 2/8 units of platelets were given in case #1/2, respectively. Lactate level increased to 25 mmol/L and decreased to 8 mmol/L in 5 hours, respectively. Both patients died in the ICU within 9 and 13 hours after admission due to bleeding. Conclusion.Extracorporeal-CPR allows vital function protection even in traumatic CA, but necessitates appropriate resuscitation. If no bleeding control is achieved, then E-CPR is futile.