Final Results of GERDA on the Two-Neutrino Double-ß Decay Half-Life of

We present the measurement of the two-neutrino double-ß decay rate of ^{76}Ge performed with the GERDA Phase II experiment. With a subset of the entire GERDA exposure, 11.8 kg yr, the half-life of the process has been determined: T_{1/2}^{2ν}=(2.022±0.018_{stat}±0.038_{syst})×10^{21} yr. This is the most precise determination of the ^{76}Ge two-neutrino double-ß decay half-life and one of the most precise measurements of a double-ß decay process. The relevant nuclear matrix element can be extracted: M_{eff}^{2ν}=(0.101±0.001).

[Molecular Mechanisms to Optimize Gene Translation Elongation Differ Significantly in Bacteria with and without Nonribosomal Peptides].

Nonribosomal peptides play an important role in the vital activity of bacteria and have an extremely broad field of biological activity. In particular, they act as antibiotics, toxins, surfactants, siderophores, and also perform a number of other specific functions. Biosynthesis of these molecules does not occur on ribosomes but by special enzymes that form gene clusters in bacterial genomes. We hypothesized that the presence of nonribosomal peptide synthesis pathways is a specific feature of bacterial metabolism, which may affect other vital processes of the cell, including translational ones. This work was the first to show the relationship between the translation regulation mechanism of protein-coding genes in bacteria, which is largely determined by the efficiency of translation elongation, and the presence of gene clusters in the genomes for the biosynthesis of nonribosomal peptides. Bioinformatic analysis of the translation elongation efficiency of protein-coding genes was performed in 11679 bacterial genomes, some of which contained gene clusters of nonribosomal peptide biosynthesis and some of which did not. The analysis showed that bacteria whose genomes contained clusters of nonribosomal peptide biosynthetic genes and those without such gene clusters differ significantly in the molecular mechanisms that ensure translation efficiency. Thus, among microorganisms whose genomes contain gene clusters of nonribosomal peptide synthetases, a significantly smaller part of them is characterized by optimized regulation of the number of local inverted repeats, while most of them have genomes optimized by the averaged energy of inverted repeats studs in mRNA and additionally by codon composition. Our results suggest that the presence of nonribosomal peptide biosynthetic pathways in bacteria may influence the structure of the overall bacterial metabolism, which is also expressed in the specific mechanisms of ribosomal protein biosynthesis.

Physiological Support of Goal-Directed Activity in Human.

The effectiveness of goal-directed human behavior and the processes underlying organization of such activity are the subjects of various biomedical studies. Here we review both classical and modern evidence on the fundamental principles of goal-directed human activity. Facts are presented about the basic mechanisms that ensure the effectiveness of goal-directed behavior and determine its physiological cost.

Erratum: First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

This corrects the article DOI: 10.1103/PhysRevLett.125.011801.

[Evaluation of the effectiveness of surgical treatment of recurrent urethral stricture].

INTRODUCTION: The recurrent course of the disease stricture is a complex problem for both the patient and the operating surgeon and requires an integrated approach to treatment only in expert centers. PURPOSE OF THE STUDY: To assess the effectiveness of methods of surgical treatment of recurrent urethral strictures. MATERIALS AND METHODS: At the University Clinic of Urology, Russian National Research Medical University named after N.I. Pirogov, an analysis of the results of surgical treatment of patients with recurrent urethral stricture from 2012 to 2020 was carried out. This work included patients who underwent surgical treatment for recurrent urethral stricture. A total of 120 men were involved in the work. The median length of the stricture was (min-max) - 2 (0.5-16 cm). In 95 (79.1%) patients, stricture of the bulbous urethra, in 15 (12.5%) - in the penile urethra, in 2 (1.7%) patients had panurethral stricture, in 6 (5.0%) - membranous urethra and in 2 (1.7%) - meatus. All patients were divided into two groups: with recurrent urethral stricture after primary DVIU (group I, n=77) and recurrent urethral stricture after primary urethroplasty (group II, n=43). Depending on the method of surgical treatment of recurrent urethral stricture, patients in group I were divided into 4 subgroups. Repeated DVIU + 3 months Autocatheterization - 16 (20.8%) patients; End-to-end urethroplasty - 37 (48.1%) patients; one-stage urethroplasty with a buccal graft or skin graft - 22 (28.6%) patients; multistage urethroplasty or perineostomy - 2 (2.5%) patients. Group II was also divided into 4 subgroups. DVIU - 17 (39.5%) patients; end-to-end urethroplasty - 6 (13.9%) patients; one-stage urethroplasty with a buccal graft or skin graft - 9 (20.9%) patients; multistage urethroplasty - 11 (16.7%) patients. Median Qmax - 4.68 ml/sec. Preoperative cystostomy was observed in 31 (25.8%) patients. RESULTS: The median follow-up was 24 months (range 12 to 76 months). Depending on the method of surgical treatment of recurrent urethral stricture, the effectiveness of DVIU according to strict indications was 75.7%. End-to-end urethroplasty showed an efficiency of -88,4%. One-stage augmentation urethroplasty had an efficiency of -77,4%, and multi-stage urethroplasty showed an efficiency of 84.6%. The IPSS value for the observation period 2 years was 2.6+/-0.9 points. The average value of Qmax at the time of observation was 19.4+/-7.1 ml/sec. The effectiveness of the treatment was 82%. During the follow-up period, a relapse was noted in 22 (18%) patients. The overall effectiveness of the treatment of recurrent urethral stricture, taking into account the treatment of recurrent cases of disease recurrence, was 97.5%. CONCLUSIONS: Urethroplasty is the treatment of choice for recurrent urethral strictures, which has been shown to be more effective than DVIU. However, the results of urethroplasty for recurrent strictures are worse than for primary strictures.

First Search for Bosonic Superweakly Interacting Massive Particles with Masses up to 1 MeV/c

We present the first search for bosonic superweakly interacting massive particles (super-WIMPs) as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-ß decay experiment which operates high-purity germanium detectors enriched in ^{76}Ge in an ultralow background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c^{2} to 1 MeV/c^{2}. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c^{2} have been set. As an example, at a mass of 150 keV/c^{2} the most stringent direct limits on the dimensionless couplings of axionlike particles and dark photons to electrons of g_{ae}<3×10^{-12} and α^{'}/α<6.5×10^{-24} at 90% credible interval, respectively, were obtained.

Final Results of GERDA on the Search for Neutrinoless Double-ß Decay.

The GERmanium Detector Array (GERDA) experiment searched for the lepton-number-violating neutrinoless double-ß (0νßß) decay of ^{76}Ge, whose discovery would have far-reaching implications in cosmology and particle physics. By operating bare germanium diodes, enriched in ^{76}Ge, in an active liquid argon shield, GERDA achieved an unprecedently low background index of 5.2×10^{-4} counts/(keV kg yr) in the signal region and met the design goal to collect an exposure of 100 kg yr in a background-free regime. When combined with the result of Phase I, no signal is observed after 127.2 kg yr of total exposure. A limit on the half-life of 0νßß decay in ^{76}Ge is set at T_{1/2}>1.8×10^{26} yr at 90% C.L., which coincides with the sensitivity assuming no signal.

[The place of riociguat in the treatment of patients with pulmonary arterial hypertension associated with systemic connective tissue diseases].

Pulmonary hypertension (PH) can develop in different systemic autoimmune rheumatic diseases (SARD), such as systemic scleroderma (SSD), systemic lupus erythematosus, rheumatoid arthritis, and mixed connective tissue disease In most cases, patients with SARD develop WHO group I PH (pulmonary arterial hypertension associated with systemic connective tissue diseases, PAH-SCTD). General prevalence of this pathology reaches 15 cases per million adults. Most cases of PAH-SCTD are induced by SSD. Survival of PAH-SCTD patients is generally lower than survival of patients with other forms of LAH. Treatment of any SARD, including in LAH, implies a complex approach using glucocorticoids, disease-modifying anti-rheumatic drugs (cyclophosphamide, methotrexate, azathioprine, and others), and genetically engineered biologics. Specific targeted therapy is indicated for most patients with PAH-SCTD. The representative of a new class (soluble guanylate cyclase (sGC) stimulators), riociguat, has been approved for the treatment of PAH. This drug has a unique double mechanism of action: (i) sGC sensibilization to endogenous nitric oxide (NO) by stabilizing the NO-sGC bond; and (ii) direct, NO-independent sGC stimulation. For patients with PAH-SCTD, riociguat is the major alternative to phosphodiesterase-5 inhibitors both as monotherapy and combination therapy.

Correlation Connections between Individual-and-Typological Features, Indices of Performance of Goal-Directed Activity, and Heart Rate Variability Parameters.

Correlation analysis of the performance of goal-directed activity and heart rate variability parameters in people with different individually-typological features was conducted on the model of endosurgical training. It was found that people with low level of intro-extroversion and neuroticism, but high index of situational anxiety were more successful during goal-directed behavior. The subjects with low level of neuroticism finished the tasks more quickly, both at the beginning and at the end of the observations. It was established that the number of mistakes in subjects with low personal anxiety on the 10th day of training was lower than in high-anxious individuals. It is shown that people with high rate of intro-extroversion are characterized by more pronounced increase in parasympathetic influences during basic endosurgical training. Hence, the achievement of the result in extroverts in these experimental conditions is provided by lower physiological penalty than in introverts. The definition of psychophysiological indices could be recommended for inclusion in the complex of measures for the assessment of proficiency in the training of endosurgeons.

[A clinical case of visceral toxocariasis as a cause of eosinophilic polyserositis].

The aim of the present report is to describe a clinical case of toxocariasis. 37-year - old man was admitted to Pirogov Municipal Clinical Hospital No.1 in Moscow. He was presented with intense generalized abdominal pain. Three months before the described hospitalization, the patient had acute bronchitis, then pneumonia. During the examination there were found hyperthermia, ascites, shortness of breath, sweating, hypereosinophilia. Patient lost 8 kilos over the last 6 months. There were arisen many hypotheses, however, after a more detailed survey about patient's life it turned out that he travelled a lot. So that the parasitosis became the main conjecture, which later was confirmed by serological tests.

Improved Limit on Neutrinoless Double-ß Decay of

The GERDA experiment searches for the lepton-number-violating neutrinoless double-ß decay of ^{76}Ge (^{76}Ge→^{76}Se+2e^{-}) operating bare Ge diodes with an enriched ^{76}Ge fraction in liquid argon. The exposure for broad-energy germanium type (BEGe) detectors is increased threefold with respect to our previous data release. The BEGe detectors feature an excellent background suppression from the analysis of the time profile of the detector signals. In the analysis window a background level of 1.0_{-0.4}^{+0.6}×10^{-3} counts/(keV kg yr) has been achieved; if normalized to the energy resolution this is the lowest ever achieved in any 0νßß experiment. No signal is observed and a new 90% C.L. lower limit for the half-life of 8.0×10^{25} yr is placed when combining with our previous data. The expected median sensitivity assuming no signal is 5.8×10^{25} yr.

Search for Neutrinoless Quadruple-ß Decay of

We report the results of a first experimental search for lepton number violation by four units in the neutrinoless quadruple-ß decay of ^{150}Nd using a total exposure of 0.19 kg yr recorded with the NEMO-3 detector at the Modane Underground Laboratory. We find no evidence of this decay and set lower limits on the half-life in the range T_{1/2}>(1.1-3.2)×10^{21} yr at the 90% C.L., depending on the model used for the kinematic distributions of the emitted electrons.

[Pineamin increased pineal melatonin synthesis in elderly people].

It was investigated the influence of polypeptide complex Pineamin on the 6-sulfatoxymelatonin (aMT6S) excretion in urine by ELISA test of 55 elderly patients with diminished melatoninsynthesis pineal gland function. Pineamin in course dose 100 mg has increased night level of aMT6S urine excretion in 1,9 times in comparison with relevant value untreated. Similar effect was obtained early for medical drug Epithalamin. Epithalamin also restored melatonin level in human and animals during aging. Thus, Pineamin and Epithalamin have similar stimulate effect on melatonin synthesis in elderly people pineal gland.

[The problem of cardiac safety of nonsteroidal anti-inflammatory drugs].

The paper considers an update on the mechanisms for the development of adverse reactions of nonsteroidal anti-inflammatory drugs on the cardiovascular system.

[Synthesis and Pharmacological Activity of N-Hetaryl-3(5)-Nitropyridines].

Reacting a number chlorosubstituted 3(5)-nitropyridine with some diazoles or 3-chloropyridazin-6-one synthesized previously undescribed various 2-, 4- or 6-substituted hetaryl-3(5)-nitropyridines. Furthermore, pyrazolyl-3-nitropyridine prepared by cyclizing hydrazinopyridine resulting from the nucleophilic substitution of chlorine in chlorosubstituted 3-nitropyridine by hydrazine. It has been shown that these compounds have moderate antibacterial activity against some pathogenic Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Escherichia coli), as well as a strong effect on protistocidal action form Colpoda steinii, surpassing clinically used reference drugs.

[Management of patients with insomnia and polymorbidity. A draft of the clinical guidelines]. / Vedenie patsientov s insomniei pri polimorbidnoi patologii. Proekt klinicheskikh rekomendatsii. Obshcherossiiskaya obshchestvennaya organizatsiya «Rossiiskoe obshchestvo somnologov¼.

Insomnia is a serious and widespread public health problem, but is often undetected and patients do not receive needed treatment. Insomnia is often comorbid with other diseases and conditions, such as arterial hypertension, type 2 diabetes mellitus, pain syndromes, anxiety and depressive disorders, etc. A separate problem is drug-induced insomnia, when patients develop symptoms due to other diseases treatments. Insomnia has a negative effect on the prognosis of comorbid diseases, including an increased risk of death, more severe disease, and decreased quality of life. The presence of sleep disorders makes it difficult to effectively treat the underlying disease, so clinical guidelines draft for the evaluation and treatment of insomnia in multimorbid patients is proposed. Diagnostic methods are reviewed and recommendations are given for the treatment of acute and chronic insomnia and features of the treatment of insomnia in multimorbid patients. A clinical algorithm has been proposed to determine treatment tactics in multimorbid patients.

[Management of patients with insomnia and polymorbidity: expert consensus]. / Vedenie patsientov s insomniei pri polimorbidnoi patologii: konsensus ekspertov.

Sleep disorders are becoming increasingly important due to the high comorbidity with other diseases and a significant impact on the patient's quality of life. Insomnia is the most common sleep disorder both in the general population and in patients with multimorbid pathology. Its prevalence in the general population is 6-15%, while in patients with somatic diseases it increases up to 20-40% and can reach 90% in patients with comorbid mental disorders. Another problem is the development of drug-induced insomnia. Insomnia has negative impact on the prognosis of comorbid diseases, including an increased risk of death, more severe disease, and a worse quality of life. The presence of sleep disorders makes it difficult to effectively treat the underlying disease, so it is extremely important to identify and correct these disorders in the early stages, therefore recommendations for the diagnosis of insomnia in polymorbid patients are proposed. Modern methods of treating acute and chronic insomnia and features of insomnia treatment in polymorbid patients are also discussed.

Search for tri-nucleon decays of 76Ge in GERDA.

We search for tri-nucleon decays of 76Ge in the dataset from the GERmanium Detector Array (GERDA) experiment. Decays that populate excited levels of the daughter nucleus above the threshold for particle emission lead to disintegration and are not considered. The ppp-, ppn-, and pnn-decays lead to 73Cu, 73Zn, and 73Ga nuclei, respectively. These nuclei are unstable and eventually proceed by the beta decay of 73Ga to 73Ge (stable). We search for the 73Ga decay exploiting the fact that it dominantly populates the 66.7 keV 73mGa state with half-life of 0.5 s. The nnn-decays of 76Ge that proceed via 73mGe are also included in our analysis. We find no signal candidate and place a limit on the sum of the decay widths of the inclusive tri-nucleon decays that corresponds to a lower lifetime limit of 1.2×1026 yr  (90% credible interval). This result improves previous limits for tri-nucleon decays by one to three orders of magnitude.

Liquid argon light collection and veto modeling in GERDA Phase II.

The ability to detect liquid argon scintillation light from within a densely packed high-purity germanium detector array allowed the Gerda experiment to reach an exceptionally low background rate in the search for neutrinoless double beta decay of 76 Ge. Proper modeling of the light propagation throughout the experimental setup, from any origin in the liquid argon volume to its eventual detection by the novel light read-out system, provides insight into the rejection capability and is a necessary ingredient to obtain robust background predictions. In this paper, we present a model of the Gerda liquid argon veto, as obtained by Monte Carlo simulations and constrained by calibration data, and highlight its application for background decomposition.

[Pulmonary hypertension in rheumatic heart disease: current approaches to diagnosis and therapy].

Pulmonary hypertension is a complex multidisciplinary problem in modern medicine. This review discusses its clinical and pathophysiological type associated with rheumatic heart disease. Current approaches to the pathogenesis and diagnosis of the disease are reflected; basic approaches to its treatment are discussed in terms of current clinical guidelines and new scientific achievements.