First Directional Measurement of Sub-MeV Solar Neutrinos with Borexino.

We report the measurement of sub-MeV solar neutrinos through the use of their associated Cherenkov radiation, performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The measurement is achieved using a novel technique that correlates individual photon hits of events to the known position of the Sun. In an energy window between 0.54 to 0.74 MeV, selected using the dominant scintillation light, we have measured 10 887_{-2103}^{+2386}(stat)±947(syst) (68% confidence interval) solar neutrinos out of 19 904 total events. This corresponds to a ^{7}Be neutrino interaction rate of 51.6_{-12.5}^{+13.9} counts/(day·100 ton), which is in agreement with the standard solar model predictions and the previous spectroscopic results of Borexino. The no-neutrino hypothesis can be excluded with >5σ confidence level. For the first time, we have demonstrated the possibility of utilizing the directional Cherenkov information for sub-MeV solar neutrinos, in a large-scale, high light yield liquid scintillator detector. This measurement provides an experimental proof of principle for future hybrid event reconstruction using both Cherenkov and scintillation signatures simultaneously.

Improved Measurement of Solar Neutrinos from the Carbon-Nitrogen-Oxygen Cycle by Borexino and Its Implications for the Standard Solar Model.

We present an improved measurement of the carbon-nitrogen-oxygen (CNO) solar neutrino interaction rate at Earth obtained with the complete Borexino Phase-III dataset. The measured rate, R_{CNO}=6.7_{-0.8}^{+2.0} counts/(day×100 tonnes), allows us to exclude the absence of the CNO signal with about 7σ C.L. The correspondent CNO neutrino flux is 6.6_{-0.9}^{+2.0}×10^{8} cm^{-2} s^{-1}, taking into account the neutrino flavor conversion. We use the new CNO measurement to evaluate the C and N abundances in the Sun with respect to the H abundance for the first time with solar neutrinos. Our result of N_{CN}=(5.78_{-1.00}^{+1.86})×10^{-4} displays a ∼2σ tension with the "low-metallicity" spectroscopic photospheric measurements. Furthermore, our result used together with the ^{7}Be and ^{8}B solar neutrino fluxes, also measured by Borexino, permits us to disfavor at 3.1σ C.L. the "low-metallicity" standard solar model B16-AGSS09met as an alternative to the "high-metallicity" standard solar model B16-GS98.

Analysis of Some Physiological and Biochemical Indices in Patients with Covid-19 Pneumonia Using Mathematical Methods.

The aim of the work was to conduct a retrospective analysis of the clinical data of patients with pneumonia caused by the SARS-CoV-2 virus, and to determine via mathematical methods the significance of some physiological and biochemical indices as predictive markers of an unfavorable outcome of the disease. A random cohort of patients with COVID-19 pneumonia numbered 209 people. Mathematical analysis addressed the physiological characteristics of patients recorded at the time of hospital admission, as well as blood coagulation parameters and those reflecting the development of an inflammatory reaction. The analyzed parameters were categorized relative to the reference ranges of physiologically normal values. Correlation analysis was carried out using categorical data on the disease outcome. The algorithms for calculating statistical characteristics, as well as results visualization, were programmed in Python. When comparing patient groups, the significance of differences between the determined parameters was assessed using the Pearson's χ2 test with Yates' correction. The study showed that the age over 50 and male sex can be considered risk factors for patients with COVID-19 pneumonia (p < 0.05). The disease outcome was found to be significantly affected by cardiovascular pathologies (p < 0.01) and to a lesser extent by diabetes mellitus (p < 0.10). There were revealed maximal correlation coefficients between the oxygen saturation level (-0.43), as well as the breathing rate (0.43), and a fatal outcome of the disease. For patients over 50 years of age, oxygen saturation below 80% at the time of hospital admission turned out to be a marker of mortality. It was shown that D-dimer blood levels above 625 ng/mL in patients over 80 years of age correlated with mortal outcomes. No correlation was found between the C-reactive protein (CRP) level and the disease outcome. The effect of corticosteroids on the disease outcome was analyzed in patients with different CRP levels. It was found that, while using corticosteroids, the mortality rate in patients with CRP ≤ 12.5 mg/L is 2.7 times higher than in those with CRP > 12.5 mg/L (p < 0.01). Thus, the use of adequate mathematical methods made it possible to define more precisely some mortality-associated physiological and biochemical indices in patients with COVID-19 pneumonia.

Combined Effect of NF-κB Inhibitor and ß2-Adrenoreceptor Agonist on Mouse Mortality and Blood Concentration of Proinflammatory Cytokines in Sepsis.

Experiments on random-bred albino mice showed that NF-κB inhibitor (BAY 11-7082) and ß2-adrenoreceptor agonist (dexmedetomidine hydrochloride) significantly reduced mouse mortality in 4 and 24 h after sepsis modeling (intraperitoneal administration of E. coli) by reducing blood levels of proinflammatory cytokines TNFα, IL-1ß, and IL-6. The combined administration of NF-κB inhibitor and ß2-adrenoreceptors agonist have an additive effect.

Role of ß2-Adrenoreceptors in Adrenergic Anti-Inflammatory Mechanism in Sepsis.

Experiments on random-bred albino mice showed that of ß2-adrenoreceptor agonist hexaprenaline sulfate significantly reduced mortality of mice from experimental sepsis (intraperitoneal administration of E. coli) in 4 and 24 h after modeling by reducing blood levels of proinflammatory cytokines TNFα, IL-1ß, and IL-6. The antagonist of ß2AR ICI-118,551 eliminated this effect.

Combined Effects of M1 Muscarinic Acetylcholine Receptor Agonist TBPB and α7n-Acetylcholine Receptor Activator GTS-21 on Mouse Mortality and Blood Concentration of Proinflammatory Cytokines in Sepsis.

Experiments on random-bred albino mice showed that M1 muscarinic acetylcholine receptor agonist (TBPB) and α7n-acetylcholine receptor agonist (GTS-21) significantly reduced mortality of mice with experimental sepsis (intraperitoneally administration of E. coli) in 4 and 24 h after modeling by reducing blood concentration of proinflammatory cytokines TNF-α, IL-1ß, and IL-6. Combined treatment with TBPB and GTS-21 determined their additive effect.

Role of α7-Nicotinic Acetylcholine Receptors of B Cells in the Immunotoxic Effect of Organophosphorus Compounds.

Experiments on white non-inbred rats demonstrated that treatment with organophosphorus compound dimethyl dichlorovinyl phosphate (DDVP) decreased T cell-independent antibody production by B cells and blood levels of IL-10 and IL-12; a similar effect was produced by GTS-21, a selective agonist of α7-nicotinic acetylcholine receptor. N-nicotinic receptor antagonist chlorisondamine in combination with DDVP partially prevented suppression of antibody production in comparison with the effect observed during intoxication with DDVP.

[EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p < 0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

Test of Electric Charge Conservation with Borexino.

Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single monoenergetic photon was obtained. This new bound, τ≥6.6×10^{28} yr at 90% C.L., is 2 orders of magnitude better than the previous limit.

[CHANGES IN THE FUNCTION OF LYMPHOCYTES AND CYTOKINE CONCENTRATION IN BLOOD CAUSED BY THE ACTION OF ATROPINE UNDER CONDITIONS OF ACUTE MALATHION INTOXICATION].

It was established in experiments on noninbred albino rats that acute intoxication with malathion (0.75 LD50) reduced the function of Th1 cells more significantly than the function of Th2 lymphocyte, decreases the activity of B cells and NK cells, blood levels of TNFa, IL-1b and IL-6, IFN-g, IL-2, and IL-4, while not significantly affecting the concentration of IL-10 and IL-13. Atropine (10 mg/kg) under conditions of acute malathion intoxication improved the function of T cells and B lymphocytes, NK cells, as well as the synthesis of immunoregulatory cytokines IFN-g, IL-2, and IL-4. At the same time, atropine in malathion intoxicated rats had no effect on suppression of the synthesis of proinflammatory cytokines TNF, IL-1g and IL-6 as well as the content of anti-inflammatory cytokines IL-10 and IL-13.

Effect of α7n-Acetylcholine Receptor Activation and Antibodies to TNF-α on Mortality of Mice and Concentration of Proinflammatory Cytokines During Early Stage of Sepsis.

Experiments on random-bred albino mice showed that activation α7n-acetylcholine receptors with anabasine (0.5 LD50) and the use of antibodies to TNF-α (1 mg/kg) 2 h before sepsis modeling significantly reduces mortality of mice from experimental sepsis (intraperitoneal injection of E. coli) due to a decrease in the blood concentration of proinflammatory cytokines TNF-α, IL-1ß, and IL-6. After combined administration of anti-TNF-α antibodies and anabasine, an additive effect was observed.

[Immune homeostasis impairment in acute carbon tetrachloride intoxicated rats corrected by administration of tocopherol acetate and unithiol].

The results of experiments on noninbred albino rats showed that the acute intoxication with carbon tetrachloride (CT) at a dose of 1 LD50 reduced the parameters of cellular immune response and function of Th1 cells more significantly than the levels of humoral immune response and Th2-lymphocyte function, decreases the blood content of immunoregulatory cytokines IFN-g, IL-2, IL-4 and anti-inflammatory cytokine IL-13, while not changing the concentration of anti-inflammatory cytokine IL-10 and increasing the concentration of pro-inflammatory cytokine IL-6. The application of unithiol, tocopherol acetate, and combinations partially restores the parameters examined. The combined effects of drugs during intoxication with CT does not exceed their separate action.

Changes in immunity parameters and blood cytokine concentrations after chronic nitrile acrylate intoxication.

Experiments on outbred albino rats showed that chronic nitrile acrylate intoxication (60 days, 0.05 LD50 per day subcutaneously) led to reduction of T-dependent humoral immune response (T-independent humoral immune response was less affected); parameters cell immunity were suppressed to a greater extent than parameters of humoral immune reactions. Equal attenuation of the functions of Th1 and Th2 lymphocytes, decrease of the blood levels of immunoregulatory, pro- and anti-inflammatory cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-13), and decrease of acetyl cholinesterase activity in thymic and splenic T lymphocytes were observed.

Dysfunction of Th1 and th2 lymphocytes and change in blood cytokine concentration at various stages of chronic intoxication with organophosphorus compounds.

Experiments on noninbred albino rats showed that a chronic exposure to organophosphorus compounds (carbophos and metaphos, 30 days, total dose 0.3 LD50) is primarily followed by a decrease in the immune reactions and IFN-γ associated with Th1 lymphocyte function (in comparison with the immune response due to activation of Th2 cells by IL-4). The concentrations of IL-2, IL-6, and IL-10 in the blood decreased after 30-day intoxication. The immune reactions associated with functional activity of Th1 and Th2 lymphocytes were shown to decrease similarly after chronic treatment with organophosphorus compounds for 60 days (total dose 0.6 LD50). This exposure was accompanied by a decrease in the concentrations of IFN-γ, IL-4, IL-2, and IL-6, but had no effect on the level of IL-10 in the blood.

[The effect of anabasine on mortality and concentration of proinflammatory cytokines in blood of mice at early stage of sepsis].

It was established in experiments on noninbred mice that activation of α-7n acetylcholine receptors (α-7n AChR) by anabasine in single doses of 1.0 and 5.0 mg/kg for 2 h before modeling sepsis (intraperitoneal injection of E. coli) cause a significant dose-dependent reduction of mortality of mice due to a decrease in the amount of proinflammatory cytokines TNF-α, IL-1ß, and IL-6 in the blood. Anabasine in single doses of 0.1 mg/kg had no significant impact on the studied parameters.

[Disturbances of the immune status during chronic intoxication with 1,2-dichloroethane and their treatment by administration of polyoxidonium].

It has been established in experiments on noninbred rats that chronic intoxication with 1,2-dichloroethane (30 days; total dose 0.9LD50; daily dose 0.03 mg/kg body weight) causes a reduction of immune responses, decreases the activity of acetylcholinesterase (AChE) of T-lymphocytes, reduces the concentration of blood cytokines (IFN-gamma, IL-2, IL-4, IL-6, while not affecting the content of IL-10), and damages to a greater degree Th1 cells as compared to Th2 lymphocytes. The administration of polyoxidonium (daily dose, 150 mg/kg, for 7 days,) partially restored the immune status, the activity of AChE T cells, and the content of cytokines in the blood.

[Microcirculation in the injured spleen by different operations in children].

43 children were operated on spleen injury: 14 were splenectomized; 29 splenectomy were completed with partial spleen tissue autotransplantation into the omentum. Changes of homeostatic system, hemoreology and immune status were followed up within 1 year after the operation, Connections between the type of the operation performed and the listed above changes were followed.

[Ryazan hospital--80 years].

In December 2011 marked 80 years of the founding of the Ryazan garrison hospital, originally housed in two buildings: "Redut housed"--a monument of architecture of the XVIII century and the former almshouses room "for the maimed in the war", was built in 1884 now Ryazan garrison hospital (from 2010--Branch No 6 FSI "in 1586 the district military hospital in the Western Military District", the Defense Ministry of Russia)--a multi-field medical preventive institution on the basis of which soldiers, military retirees, family members and military retirees from Ryazan, Moscow, Tambov regions are treated. Every year more than 7 thousand patients get treatment here. During the counterterrorism operations in Chechnya over 800 wounded were brought to the hospital from the battle area.

[Diagnostic criteria, epidemiology and substantiation of clinicopathogenetic types of perioral dermatitis].

The perioral dermatitis is a multifactorial disease of a face skin meeting in population with frequency of 5% also represents inflammatory process with the various morphological characteristic of an eruption. A total of 511 patients are surveyed by a perioral dermatitis. For the first time clinico-pathogenetic types of development and a disease current (it is hormonal--immunologic, allergic, gastroenterology, metabolic) with characteristic distinctive changes of the hormonal status, a metabolism and immunity system are allocated. The complex of laboratory criteria of diagnostics of the specified types of the perioral dermatitis, giving representation about mechanisms of formation, clinical features of the dermatosis is developed, allowing differentiate to prove the approach to treatment.