Logistic regression model for predicting failure of dual antihypertensive therapy: a prospective comparative non-randomized clinical trial

Background. Initial dual antihypertensive therapy is currently considered as the first management step for the majority of patients with arterial hypertension. However, it often fails to achieve the target blood pressure levels. An approved algorithm for predicting the failure of dual antihypertensive therapy is still to be developed. Objectives. To establish predictors of dual antihypertensive therapy failure in patients with high and very high cardiovascular risk and to create a model for predicting negative outcome of dual antihypertensive therapy. Methods. The paper presents a prospective comparative non-randomized clinical trial. The recruiting of participants and recording of results were carried out in March–December 2019 with 3 months of the follow-up period. The trial involved examination of 88 patients with poor blood pressure control, stage II and III arterial hypertension, high and very high cardiovascular risk of stages 1–3. Clinical and laboratory examination was carried out in compliance with the current regulatory documents. Additional examination included tests for uric acid, high-sensitivity C-reactive protein, as well as respiratory polygraphy and computerized capillaroscopy. All patients were prescribed dual antihypertensive therapy. The primary search for predictors was performed using the binary logistic regression. The predictive model was developed by stepwise variable selection. The diagnostic significance of the binary classifier was assessed by means of ROC-curve analysis; the calculation was performed using MedCalc 20.218 software (MedCalc Software Ltd., Belgium). Results. Administration of two hypotensive drugs appears to be effective in 33% of patients. The final model for predicting negative outcomes of dual antihypertensive therapy included such independent predictors as interventricular septal thickness, daily mean systolic blood pressure, and area density of the capillary network. The odds ratio accounted for 9.1 (95% confidence interval 3.12; 26.82). The area under the ROC curve based on the multiple binary logistic regression model comprised 0.805±0.05 with 95% confidence interval: 0.707-0.882 (p<0.0001). The sensitivity and specificity of the method amounted to 83.1 and 69.0%, respectively. The prediction accuracy comprised 77.3%. Conclusion. The development of patient-oriented algorithms for selection of hypotensive treatment is considered to be essential due to poor blood pressure control during dual antihypertensive therapy. The developed prognostic model may be applied when managing hypertension

First measurement of the T-violating muon polarization in the decay K^+ --> mu^+ nu gamma

We present the result of the first measurement of the T-violating muon polarization P_T in the decay K^+ --> mu^+ nu gamma. This polarization is sensitive to new sources of CP-violation in the Higgs sector. Using data accumulated in the period 1996-98 we have obtained P_T = (-0.64 +- 1.85(stat) +- 0.10(syst))x10^{-2} which is consistent with no T-violation in this decay.Comment: 11 pages, 8 figure

A new limit of T-violating transverse muon polarization in the K+→π0μ+νK^{+}\to\pi^{0}\mu^{+} \nu decay

A search for T-violating transverse muon polarization ($P_T$) in the $K^{+}\to \pi^{0}\mu^{+}\nu$ decay was performed using kaon decays at rest. A new improved value, $P_T= -0.0017\pm 0.0023 (stat)\pm 0.0011 (syst)$, was obtained giving an upper limit, $| P_T | < 0.0050$. The T-violation parameter was determined to be Im$\xi = -0.0053 \pm 0.0071(stat)\pm 0.0036(syst)$ giving an upper limit, $|$Im$\xi| <0.016$.Comment: 5 pages, 4 figure

Ribosomal DNA as DAMPs Signal for MCF7 Cancer Cells

Introduction: The cell free ribosomal DNA (cf-rDNA) is accrued in the total pool of cell free DNA (cfDNA) in some non-cancer diseases and demonstrates DAMPs characteristics. The major research questions: (1) How does cell free rDNA content change in breast cancer; (2) What type of response in the MCF7 breast cancer cells is caused by cf-rDNA; and (3) What type of DNA sensors (TLR9 or AIM2) is stimulated in MCF7 in response to the action of cf-rDNA?Materials and Methods: CfDNA and gDNA were isolated from the blood plasma and the cells derived from 38 breast cancer patients and 20 healthy female controls. The rDNA content in DNA was determined using non-radioactive quantitative hybridization. In order to explore the rDNA influence on MCF7 breast cancer cells, the model constructs (GC-DNAs) were applied: pBR322-rDNA plasmid (rDNA inset 5836 bp long) and pBR322 vector. ROS generation, DNA damage, cell cycle, expression of TLR9, AIM2, NF-kB, STAT3, and RNA for 44 genes affecting the cancer cell viability were evaluated. The methods used: RT-qPCR, fluorescent microscopy, immunoassay, flow cytometry, and siRNA technology.Results: The ratio R = cf-rDNA/g-rDNA for the cases was higher than for the controls (median 3.4 vs. 0.8, p &lt; 10−8). In MCF7, GC-DNAs induce a ROS burst, DNA damage response, and augmentation of NF-kB and STAT3 activity. The number of the apoptotic cells decreases, while the number of cells with an instable genome (G2/M– arrest, micronuclei) increase. Expression of anti-apoptotic genes (BCL2, BCL2A1, BCL2L1, BIRC3, MDM2) is elevated, while expression of pro-apoptotic genes (BAX, BID, BAD, PMAIP1, BBC3) is lowered. The cells response for pBR322-rDNA is much more intense and develops much faster, than response for pBR322, and is realized through activation of TLR9- MyD88 - NF-kB- signaling. This difference in response speed is owing to the heightened oxidability of pBR322-rDNA and better ability to penetrate the cell. Induction of TLR9 expression in MCF7 is followed by blocking AIM2 expression.Conclusion: (1) Ribosomal DNA accumulates in cfDNA of breast cancer patients; (2) Cell free rDNA induce DNA damage response and stimulates cells survival, including cells with an instable genome; (3) Cell free rDNA triggers TLR9- MyD88- NF-kB- signaling, with significantly repressing the expression of AIM2

Study of high-frequency magnetic properties of composites and multi-layer films

This paper examines the high-frequency magnetic properties of heterogeneous nanogranular composites (Co45Fe45Zr10)X(Al2O3)100-X, obtained by ion-beam sputtering of composite target on the sitallic substrates. It is shown that in the region of metallic phase concentrations from 32 to 42 at. % μ/ and μ// have high values, which are significantly higher than those of bulk composites of similar composition. As the composite layers approach the threshold, both the real and imaginary portions of the complex magnetic permeability decrease

Synthesis and dielectric properties of metal-ceramic nanostructures

In this work, electrical properties of metal-dielectric nanocom-posites with amorphous structure and multilayer films based on them have been investigated. It is shown that the concentration dependences of the electrical resistance of the composites have a S-shaped form following from the model of percolation conduction theory with the threshold in the region of concentrations ~ 40-60 % in total of the metal component. Meth-ods for the preparation of heterogeneous nanosystems are also described

Increased Transfection of the Easily Oxidizable GC-Rich DNA Fragments into the MCF7 Breast Cancer Cell

Objective. Easily oxidizable GC-rich DNA (GC-DNA) fragments accumulate in the cell-free DNA (cfDNA) of patients with various diseases. The human oxidized DNA penetrates the MCF7 breast cancer cells and significantly changes their physiology. It can be assumed that readily oxidizable GC-DNA fragments can penetrate the cancer cells and be expressed. Methods. MCF7 cells were cultured in the presence of two types of GC-DNA probes: (1) vectors pBR322 and pEGFP and (2) plasmids carrying inserted human rDNA (pBR322-rDNA and pEGFP-rDNA). pEGFP and pEGFP-rDNA contained a CMV promoter and a fluorescent protein gene EGFP. ROS generation rate, accumulation of the DNA probes in MCF7, 8-oxodG content, expression of EGFP and NOX4, and localization of EGFP, NOX4, and 8-oxodG in MCF7 were explored. The applied methods were qPCR, fluorescent microscopy (FM), immunoassay, and flow cytometry (FCA). Results. When GC-DNA is added to the cell culture medium, it interacts with the cell surface. At the site of GC-DNA contact with the cell, NOX4 is expressed, and ROS level increases. The ROS oxidize the GC-DNA. When using the plasmids pEGFP and pEGFP-rDNA, an increase in the amount of the DNA EGFP, RNA EGFP, and EGFP proteins was detected in the cells. These facts suggest that GC-DNA penetrates the cells and the EGFP gene is expressed. Insertions of the rDNA significantly increase the GC-DNA oxidation degree as well as the rate of plasmid transfection into the cells and the EGFP expression level. In the nucleus, the oxidized GC-rDNA fragments, but not the vectors, are localized within the nucleolus. Conclusions. GC-rich cfDNA fragments that are prone to oxidation can easily penetrate the cancer cells and be expressed. The cfDNA should become a target for the antitumor therapy

Further search for T-violation in the decay K+ -> pi(0)mu(+)nu

A new result for the transverse mu(+) polarization, P-T, in the decay K+ --> pi(0)mu+nu has been obtained in the KEK E246 experiment. Combined with our earlier result, P-T = (-1.12 +/- 2.17(stat) +/- 0.90(syst)) X 10(-3) and Im(xi) = (-0.28 +/- 0.69(stat) +/- 0.30(syst)) X 10(-2), which are consistent with no T-violation