[Levilimab and baricitinib prescribing experience in outpatient COVID-19 patients' treatment].

AIM: To study the effect of levilimab or baricitinib in combination with standard therapy (ST) on the incidence of severe viral pneumonia associated with a new coronavirus infection COVID-19. MATERIALS AND METHODS: A multicenter, open-label observational study of the efficacy and safety of levilimab in combination with ST (group 1, n=100), baricitinib in combination with ST (group 2, n=139), or in comparison with ST (group 3, n=200) in outpatients with verified CT-1 pneumonia. RESULTS: According to the results of laboratory tests, patients treated with levilimab in combination with ST had the best dynamics of changes in CRP from reliably the highest level (mg/L) to the lowest in comparison with other groups. In the group of patients with ST, in contrast to the other groups, no dynamics of CRP was observed by day 5 of therapy. In group of hospitalized patients initially receiving levilimab in addition to ST, the rate of transfer to the intensive care unit (2 patients, 9.52%) and length of stay (4 days) was significantly lower compared to the values in patients in both the baricitinib group in combination with ST (7 patients, 15.56%; 5 days [interquartile range 36.5]) and in patients receiving ST alone (7 patients, 15.56%; 5 days [interquartile range 36.5]). Also in hospitalized patients we observed no statistically significant intergroup differences in the incidence of infectious complications and thromboembolic events, which confirms the safety of including levilimab or baricitinib in COVID-19 pathogenetic therapy regimens. Observational results support the hypothesis that the initial inclusion of levilimab or baricitinib in addition to ST is accompanied by a reduced risk of viral pneumonia progression. CONCLUSION: The addition of levilimab or baricitinib to the therapy regimen for coronavirus infection during the outpatient phase has demonstrated a preemptive anti-inflammatory effect and reduced the probability of lung tissue damage progression.

The influence of blood phenylalanine levels on neurocognitive function in adult PKU patients.

It is well known that hyperphenylalaninemia caused by phenylketonuria (PKU) negatively influences cognitive performance. Several tests have been used to study these functions. Until now, no universal, optimal tool has been developed for detecting PKU-caused brain dysfunctions. Using computerized neuropsychological tests during daily routine would be helpful for screening subclinical brain deficits in adult PKU patients. In a monocentric, cross-sectional study, adult patients with PKU (n = 46; median age = 29.5 years; female/male ratio = 21/25) were tested with the computerized Cambridge Cognition (CANTAB) test measuring neurocognitive functions. Patients were divided into two groups: The "on diet" group included patients whose blood Phe-level was under 600 µmol/l (n = 20), and the "loose diet" group included patients whose blood Phe-level was above 600 µmol/l (n = 26) at the examination time. The results of the PKU-affected individuals were compared with a healthy control group (n = 31; median age = 25 years; female/male ratio = 11/20). Compared with the control group, PKU patients had significantly worse test results in memory, problem-solving skills, and strategy. However, there were no significant differences in response speed or initial thinking time. There was no correlation between the blood Phe-level, tyrosine (Tyr)-level or Phe/Tyr ratio and the different cognitive test results. There were no significant differences in test results between the two PKU subgroups. Several cognitive functions measured by CANTAB are negatively influenced by hyperphenylalaninemia in adult PKU patients. However, response speed and initial thinking time were not impaired as seriously as other functions. Patients with lower Phe-levels failed to achieve better test results than patients whose Phe-levels were notably elevated.

Development and evaluation of a RT-qPCR assay for fast and sensitive rabies diagnosis.

Rabies virus is endemic to Russia, among other countries. It is therefore critical to develop a high-quality and high-precision diagnostic procedure for the control and prevention of infection. The main objective of the research presented here was to develop a reliable RT-qPCR assay for rabies diagnostics. For this purpose, a RABV strains from various biological and geographical origins were used. In addition, rabies-positive and rabies-negative samples, as well as nucleic acids from other viruses and DNA extracted from the brain tissues of mice, dogs, cats, bats and humans, were studied using the developed assay. The analytical sensitivity of the assay, as assessed using armored recombinant positive control dilutions, was 103 copies/ml, and the sensitivity measured using characterized strains was between 0.1 LD50/ml and 1.0 LD50/ml. A broad range of RNA from RABV strains circulating in different regions of Russia, as well as RNA from RABV-positive primary brain samples from 81 animals and two humans, was detected using the developed assay. No false-positive or false-negative results were obtained. Given that high analytical and diagnostic sensitivities and a high specificity were verified for this assay, it has high potential as a screening test that may be suitable for the epizootiological monitoring of animals and for the fast postmortem diagnosis of rabies.

The burden of tick-borne diseases in the Altai region of Russia.

This article presents the results of a comprehensive survey of the burden of tick-borne infectious diseases (TBIDs) in the Altai region of Russia. Official data for TBID incidence were analyzed and 201 samples from patients with suspected TBID were studied. Furthermore, questing ticks and ticks recovered from humans were examined to estimate prevalence of TBID-causative agents. The Altai region was determined to have a heightened risk for TBIDs in Russia. The most epidemiologically significant tick-borne illness in this area is spotted fever group rickettsiosis, while nationally in Russia, the leading TBID is Lyme borreliosis. The prevalence of mixed infection was 12.4% among the studied cases. Additionally, the prevalence of poorly studied pathogens - Kemerovo virus (KEMV) and Rickettsia tarasevichiae - in ticks from the Altai region was determined.

[The clinical effectiveness of the application of interferential currents for the combined treatment of onychopathies associated with psoriasis and eczema]. / Klinicheskaya effektivnost' primeneniya interferentsionnykh tokov v kompleksnom lechenii onikhopatii pri psoriaze i ekzeme.

The frequency of the development of clinically significant changes in the nail plates was estimated in the present study that included 454 patients presenting with psoriasis and 140 patients with eczema characterized by the localization of the pathological process on the skin of the wrists and/or feet. The changes in the nail plates were shown to occur in 56,2% of the patients with psoriasis and in 90,7% of those suffering from eczema. The capillaroscopy of the microvessels feeding the affected nails was carried out to determine the type of the capillaroscopic picture. The patients with onychopathies were largely characterized by the spastic-atonic type of the changes in the microcirculatory bed. The changes of this type were documented in 86,5% of the patients with psoriatic onychopathy and in 83,9% of those presenting with onychodystrophy associated with eczema. The effectiveness of the combined treatment including the application of interferential currents was estimated in comparison with that of standard therapy. It was shown that the use of interferential currents for the treatment of the patients with psoriasis results in a decrease of the severity index of nail damage by 47,8% in comparison with 18,1% in the case of standard medicamentous therapy. Similarly, a 77,2 and 51,3% decrease of the index of severity was documented in the patients with eczema after their treatment with the use of interferential currents and standard medicamentous therapy, respectively.

[Scientific substantiation of sizes of sanitary protection zones of anthrax burial sites based on the comprehensive evaluation of risk factors].

In the Russian Federation anthrax epizootics are still being registered among animals as well as epidemic foci of the population. This situation is linked to natural reservoirs of the pathogen - numerous anthrax burial sites which belong to class I of dangerous objects. In this connection, a one-kilometer sanitary protective zone is required according to current Russian Federation legislation. As a result, a significant land of the country is unsuitable for any agricultural use. Meanwhile, epizootologo-epidemiological observations indicate to that different anthrax burial sites differ in their characteristics and represent varying degrees of the risk. In connection with the development of the agricultural sector, intensive construction and the development of new and abandoned areas there is a need of creating unified approaches to assess the risk of anthrax burial sites, as well as to determine the size of sanitary protection zones based on the risk assessment. This article represents an original methodology to assess the actual danger of anthrax burial sites. It is based on a comprehensive multi-factor quantity-related risk assessment, described by a model that accounting the importance of each study for natural, social and biological factors. Undertaking this methodology allowed to reveal a degree of danger of anthrax burial sites located in different territories of the Russian Federation, and helped to substantiate the dimensions of their sanitary protection zones.

[CONTEMPORARY EPIZOOTOLOGICAL AND EPIDEMIOLOGICAL FEATURES OF BRUCELLOSIS IN THE REPUBLIC OF TAJIKISTAN].

AIM: Study epizootological and epidemiological features of brucellosis on the territory of the Republic of Tajikistan under the conditions of social-economic transformation with evaluation of width and scale of its spread, as well as reasons of the present situation. MATERIALS AND METHODS: Official statistics data, results of expert evaluations, reports, analytical material of national and international organizations, results of clinical and epidemiological analysis were used. Descriptive- evaluative epidemiologic methods, serologic studies of samples obtained from humans, animals, environmental objects between 2000 and 2013; mapping using GIS-technology, as well as statisti- cal analysis were used. Techniques of calculation of DALY-index and population infection risk parameter were used. RESULTS: Features of situation by brucellosis were detected, that lay in its wide spread among humans and agricultural animals, changes in morbidity structure, as well as char- acter of its seasonal and territorial spread, connected with predominant effect of social risk factors. CONCLUSION: Contemporary situation for brucellosis in the Republic of Tajikistan is characterized by a pronounced non-welfare and determined by acting social-economic conditions. The main factors are changes in the conditions of conducting agricultural activity against the background of high level of unemployment and external work migration.

Histophysiology of the immune system of Wistar rats at delayed terms after ovariectomy.

We studied histophysiological changes in organs of the immune system, liver, and lungs of Wistar rats at delayed terms after ovariectomy. On day 52 after surgical castration leading to a decrease in estradiol, progesterone, and testosterone levels, activation of the immune system was revealed characterized by stage I accidental thymus involution, while pulp depletion in the spleen, and enhanced IL-2 and IFN-γ production. We also observed small-droplet degeneration of hepatocytes and reactive changes in the lungs manifested in increased number of neutrophils in the interalveolar septa.

Gender differences in pulmonary and immune response in acute experimental endotoxicosis.

Differences in the immune and inflammatory response were revealed in the lungs of male and female Wistar rats on day 1 after administration of LPS in a dose inducing the development of acute bacterial endotoxemia. Females showed more pronounced morphofunctional signs of immune system activation than males: this was characterized by more severe accidental involution of the thymus, devastation of the splenic white pulp, and enhanced production of IL-4, IL-12, and TNF-α by splenocytes. In males, production of the above cytokines decreased and inflammation in the lungs was more pronounced at these terms.

[Anthrax cattle burial grounds in Russia and their biosafety].

AIM: To develop standard operating procedure for assessment level of biohazard for population living near existing cattle burial grounds. MATERIALS AND METHODS: Development of standard operating procedure for assessment of biosafety of cattle burial grounds was performed on the basis of regulatory documents and regional field practical experience. Assessment of biohazard level of anthrax cattle burial grounds was performed in 5 regions choosen on the basis of certain criteria. Total number of samples taken was 762. RESULTS: Rating of federal districts according to number of permanently problematic on anthrax places was composed. It was determined that maximal number of permanently problematic on anthrax places was active during time period until 1950. Agent of anthrax was not detected in studied samples either as spores or vegetative forms and soil was categorized as "clean" on all indicators. CONCLUSION: It was determined that conditions of burial of cattle fallen due to anthrax and their maintenance rules are followed in 5 places. All cattle burial grounds are located inside towns' borders or adjoin to areas of existing or planned apartment blocks.