Personalized management of hypertensive patients: focus on prognostic biomarkers

Aim. To analyze level of circulating biomarkers of plasma vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) during 3-month therapy with a fixed-dose combination of ramipril/indapamide (Konsilar-D24, AO Vertex, Russia), as well as to evaluate the antihypertensive efficacy of a fixed-dose combination of ramipril/indapamide (Konsilar-D24, JSC “Vertex”, Russia) in hypertensive (HTN) patients with type 2 diabetes (T2D).Material and methods. This prospective open-label study included 44 patients (aged 35 to 60 years) of both sexes with essential grade 1-2 HTN and concomitant compensated T2D, who did not reach the target blood pressure (BP) level using single or dual antihypertensive therapy, as well as patients who did not take antihypertensives. All patients included in the study initially underwent a set of standard clinical, laboratory and functional examinations in accordance with the clinical guidelines for the management of patients with HTN and T2D, as well as an assessment of the level of C-reactive protein, VEGF and TNF-α. Patients were monitored and treated with Konsilar-D24 for 3 months.Results. In 93,2% of patients, individual target BP values were achieved during the first 2-4 weeks of therapy with a fixed combination of ramipril/indapamide (Konsilar-D24). In the subsequent 3-month follow-up, the average daily BP level in all patients ranged from 129/79 mm Hg to 110/70 mm Hg. Three-month Konsilar-D24 therapy showed a decrease in microalbuminuria: the median values of microalbuminuria decreased by 2 times, and the decrease in the maximum recorded values reached 40% of the baseline. Decrease in mean TNF-α values after 3-month therapy with Konsilar-D24 was 33% of the baseline values, while the maximum recorded values during the specified period decreased by 17%. Decrease in median VEGF values after 3-month Konsilar-D24 therapy was 28%, while the maximum value decreased by 7%, the minimum — by 8%.Conclusion. Konsilar-D24 improves the prognosis in hypertensive patients not only by reducing BP to target values, but also by reducing the level of VEGF and TNF-α biomarkers that determine the progression of endothelial dysfunction, diabetic retinopathy, and microalbuminuria

Features of the functional activity of macrophage link of immunity with gastroesophageal reflux disease depending on the type of reluctate: in vitro model

Aim. A generalized analysis of changes in functional activity of macrophages on the basis of phagocytic activity, cytokine profile, changes in the level of expression of surface markers characteristic of pro - or anti-inflammatory phenotype of the cells when exposed to reluctate. Materials and methods. Developed in vitro model of co-peritoneal macrophages of mice With57/BL6 (n=65) and reluctate patients with gastroesophageal reflux disease (GERD; n=65) having different pH values (three group comparison). Took into account the standard criteria phagocytic ability (absorption Staphylococcus aureus 9198, light microscopy), secretory activity (cytokine profile Th1/Th2, flow cytometry) and receptor characterization of macrophages (expression of CD25/80/163/206, flow cytometry). Results. The phagocytic activity of macrophages, calculated on the basis of the average number of bacteria ingested by one phagocyte, is not associated with the pH value of the added reluctate. It is established that the alkalinisation of reluctate leads to significant alteration in the expression of CD receptors - decrease M1 and increase M2. The index of total production of Th1/Тһ2 in groups progressively decreased with increasing pH of reluctate and amounted to 3.6 units in the group pH from 4.6 to 6.6; 2.8 units group a pH of 6.7-7.2 and 1.6 units in the group pH of 7.3 to 8.1, due to increased production of Th2 cytokines at offset reluctate pH to slightly alkaline side. The data obtained indicate the increase of expression and secretion of anti-inflammatory markers at an alkaline pH shift of reluctate. Analysis of the studied characteristics of the activity profile of macrophages in the proposed in vitro model justifies the need for considering the peculiarities of the functional activity of macrophages under the influence of reluctate different nature. The special importance of studying the cytokine profile and characteristics of the functional activity of macrophages in patients with GERD, given the nature of reluctate

Fano Effect in a Few-Electron Quantum Dot

We have studied the Fano effect in a few-electron quantum dot side-coupled to a quantum wire. The conductance of the wire, which shows an ordinal staircase-like quantization without the dot, is modified through the interference (the Fano effect) and the charging effects. These effects are utilized to verify the exhaustion of electrons in the dot. The "addition energy spectrum" of the dot shows a shell structure, indicating that the electron confinement potential is fairly circular. A rapid sign inversion of the Fano parameter on the first conductance plateau with the change of the wire gate voltage has been observed, and explained by introducing a finite width of dot-wire coupling.Comment: 11 pages, 7 figure

Macrophage phenotype after human refluxate exposure, esophageal dysmotility and their correlation with gastroesophageal reflux disease

Aim of the study. To investigate the esophageal dysmotility, changes in the esophageal mucosa and the immune response depending on the type of refluxate in gastroesophageal reflux disease (GERD) patients.Material and methods. 68 patients with GERD were recruited: 28 (14 men; mean age, 45.74 ± 2.23 years) nonerosive reflux disease (NERD), 22 (15 men; mean age, 45.0 ± 3.24 years) erosive reflux disease (EE), 18 (13 men; mean age, 47.22 ± 2.95) Barrett’s Esophagus (BE). GERD patients underwent esophageal high-resolution manometry (HRM) with a 22-channel water-perfused catheter and Solar GI system (Medical Measurements Systems, Enschede, the Netherlands), 24-hour impedance and pH monitoring using the Ohmega Ambulatory Impedance pH Recorder (Medical Measurements Systems). We analyzed receptor characteristics of monocyte-derived macrophages in all groups of patients.Results. On HRM examination, we showed that DCI (distal contractile integral) in NERD patients was higher than in EE (p = 0.088) and BE (p = 0.076), also LES RP (lower esophageal sphincter resting pressure) in NERD patients was higher than in EE (p = 0.039) and BE (p = 0.012). The analysis of reflux characteristics showed that the total reflux time with pH < 4 for BE patients was longer than that for NERD and EE patients. An analysis of receptor characteristics of monocyte-derived macrophages showed the prevalence of CD25 and CD80 expression in all groups of patients.Conclusion. An analysis of the phenotype of macrophages derived from blood monocytes of GERD patients revealed a prevalence of М1 macrophages that was typical for the Th1 type of immune response. The degree of esophageal dysmotility was correlated with GERD severity and type

Magnetophotonic intensity effects in hybrid metal-dielectric structures

The magneto-optical properties of a hybrid metal-dielectric structure consisting of a one-dimensional gold grating on top of a magnetic waveguide layer are studied experimentally and theoretically. It is demonstrated that a magnetic field applied in the longitudinal configuration (in the plane of the magnetic film and perpendicular to the slits in the gold grating) to the metal-dielectric structure modifies the field distribution of the optical modes and thus changes the mode excitation conditions. In the optical far field, this manifests in the alteration of the optical transmittance or reflectance when the structure becomes magnetized. This magneto-optical effect is shown to represent a novel class of effects related to the magnetic-field-induced modification of the Bloch modes of the periodic hybrid structure. That is why we define this effect as longitudinal magnetophotonic intensity effect (LMPIE). The LMPIE has two contributions, odd and even in magnetization. While the even LMPIE is maximal for the light polarized perpendicular to the grating slits (TM) and minimal for the orthogonal polarization (TE), the odd LMPIE takes maximum values at some intermediate polarization and vanishes for pure TM and TE polarizations. Two principal modes of the magnetic layer - TM and TE - acquire in the longitudinal magnetic field additional field components and thus turn into quasi-TM and quasi-TE modes, respectively. The largest LMPIE is observed for excitation of the antisymmetrical quasi-TE mode by TM-polarized light. The value of the LMPIE measured for the plasmonic structure with a magnetic film of Bi2Dy1Fe4Ga1O12 composition is about 1% for the even effect and 2% for the odd one. However, the plasmonic structure with a magnetic film with a higher concentration of bismuth (Bi2.97Er0.03Fe4Al0.5Ga0.5O12) gives significantly larger LMPIE: even LMPIE reaches 24% and odd LMPIE is 9%. Enhancement of the magneto-optical figure of merit (defined as the ratio of the specific Faraday angle of a magnetic film to its absorption coefficient) of the magnetic films potentially causes the even LMPIE to exceed 100% as is predicted by calculations. Thus, the nanostructured material described here may be considered as an ultrafast magnetophotonic light valve

Feature integration in natural language concepts

Two experiments measured the joint influence of three key sets of semantic features on the frequency with which artifacts (Experiment 1) or plants and creatures (Experiment 2) were categorized in familiar categories. For artifacts, current function outweighed both originally intended function and current appearance. For biological kinds, appearance and behavior, an inner biological function, and appearance and behavior of offspring all had similarly strong effects on categorization. The data were analyzed to determine whether an independent cue model or an interactive model best accounted for how the effects of the three feature sets combined. Feature integration was found to be additive for artifacts but interactive for biological kinds. In keeping with this, membership in contrasting artifact categories tended to be superadditive, indicating overlapping categories, whereas for biological kinds, it was subadditive, indicating conceptual gaps between categories. It is argued that the results underline a key domain difference between artifact and biological concepts

Plasmon-mediated magneto-optical transparency

Magnetic field control of light is among the most intriguing methods for modulation of light intensity and polarization on sub-nanosecond timescales. The implementation in nanostructured hybrid materials provides a remarkable increase of magneto-optical effects. However, so far only the enhancement of already known effects has been demonstrated in such materials. Here we postulate a novel magneto-optical phenomenon that originates solely from suitably designed nanostructured metal-dielectric material, the so-called magneto-plasmonic crystal. In this material, an incident light excites coupled plasmonic oscillations and a waveguide mode. An in-plane magnetic field allows excitation of an orthogonally polarized waveguide mode that modifies optical spectrum of the magneto-plasmonic crystal and increases its transparency. The experimentally achieved light intensity modulation reaches 24%. As the effect can potentially exceed 100%, it may have great importance for applied nanophotonics. Further, the effect allows manipulating and exciting waveguide modes by a magnetic field and light of proper polarization

SOME FEATURES OF CURRENT TECHNOGENIC MOVEMENTS OF THE EARTH’S CRUST

We describe the history of studying the current crustal movements by various methods and discuss technogenic effects recorded at large water-reservoir zones and mineral deposits in Siberia. Initially, classical surveying techniques aimed to obtain high-accuracy ground-based measurements of height, tilt and direction. Modern geodesy techniques and methods for measuring absolute gravity are now available to investigate displacement, deformation, tilt and other phenomena taking place on the Earth’s surface. These methods are used to estimate kinematic parameters of the crust areas (e.g. rates of subsidence and horizontal movements) and to monitor fluid motions in mineral deposits. Such data are critical for ensuring a proper management of the mineral deposits. In this article, we analyse technogenic processes observed in the Ust Balyk oil-gas field, the Zapolyarny gas deposit, the water-reservoir zone at the Sayano-Shushenskaya hydroelectric power station (SSHPS) on the Yenisei river, and large open-pit mines in the Kuzbass basin. Our analysis is based on surface displacement rates estimated from the data collected in different periods of observations at large man-made facilities. In the study of the hydro technical objects, we estimated the displacement rates at 5.0 mm per year. In the northern areas of the West Siberian petroleum basin, subsidence rates amounted to 20–25 mm per year in the early 2000s. These estimates were supported by the high-accuracy gravity measurements showing an increase up to 6–7 microGal per year in the oil-gas field development areas. We assess a possibility of triggering effects related to weak seismicity due to a high stress accumulation rate (1 KPa per hour) in the SSHPS area. A connection between earth tides and catastrophic events, such as gas emissions in high amounts on mining sites, is discussed. Having analysed the surface monitoring records taken in South Primorye in September 2017, we conclude that underground nuclear explosions in North Korea in this period did not cause any significant displacement of the surface in this most southerly region of the Russian Far East territories

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified