[Vaping and vaping-associated lung injury: A review].

Vaping, i.e. the use of electronic nicotine/other substances delivery systems, increases a risk of vaping-associated lung injury. The review describes clinical manifestation, methods of diagnosis and diagnostic criteria, treatment of patients with this disease as well as risk stratification of vapers and approaches to their management based on Worchester classification and clinical guidance. The pathogenetic mechanisms of vaping-associated lung injury have been analyzed.

Electrical Discharge in a Cavitating Liquid under an Ultrasound Field.

A theoretical model for an electrical discharge in a cavitating liquid is developed and compared with experiments for the optimization of the water treatment device. The calculations based on solution of the Noltingk─Neppiras equation support the hypothesis that the electric field promotes the formation of vapor microchannels inside a liquid gap between the electrodes, where at a low gas pressure Paschen's conditions of rupture and abnormal glow discharge maintenance in those microchannels are fulfilled. Theoretical analysis of the cavitation processes and the discharge formation processes is in qualitative agreement with the experimental data obtained in this work in a water treatment device using a hydrodynamic emitter. The following graphic illustrates the experimental setup: (1) feeding tank, (2) hydrodynamic emitter, (3) zone of cavitation inside the plasma reactor, (4) high-frequency generator of electric impulses, and (5) outlet.

Differences in the Differentiation Potential and Relative Levels of Gene Expression in the Bone Marrow-Derived Fibroblast Colony-Forming Units in Patients during the Onset of Aplastic Anemia Depending on the Disease Severity.

The differentiation potential of individual clones of fibroblast CFU (CFU-F) was studied and the relative expression level of genes was analyzed in the culture of CFU-F from the bone marrow in patients with non-severe and severe forms of aplastic anemia at the onset of the disease. The differentiation potential of CFU-F clones was determined by the relative expression of marker genes using quantitative PCR. In aplastic anemia, the ratio of CFU-F clones with different differentiation potential changes, but the molecular mechanisms of this phenomenon are different in non-severe and severe aplastic anemia. In the culture of CFU-F in non-severe and severe aplastic anemia, the relative expression level of genes associated with the maintenance of the hematopoietic stem cell in the bone marrow niche changes, but the decrease in the expression of immunoregulatory genes occurs in severe form only, which may reflect differences in the pathogenesis of non-severe and severe aplastic anemia.

Fluorescent polymer markers photoconvertible with a 532 nm laser for individual cell labeling.

Fluorescent photoconvertible materials and molecules have been successfully exploited as bioimaging markers and cell trackers. Recently, the novel fluorescent photoconvertible polymer markers have been developed that allow the long-term tracking of individual labeled cells. However, it is still necessary to study the functionality of this type of fluorescent labels for various operating conditions, in particular for commonly used discrete wavelength lasers. In this article, the photoconversion of fluorescent polymer labels with both pulsed and continuous-wave lasers with 532 nm-irradiation wavelength, and under different laser power densities were studied. The photoconversion process was described and its possible mechanism was proposed. The peculiarities of fluorescent polymer capsules performance as an aqueous suspension and as a single capsule were described. We performed the successful nondestructivity marker photoconversion inside RAW 264.7 monocyte/macrophage cells under continuous-wave laser with 532 nm-irradiation wavelength, showing prospects of these fluorescent markers for long-term live cell labeling.

Age and Sex Characteristics of the Blood Cytokine Profile in Rats Subjected to Prenatal Stress.

Parameters of blood cytokine profile in male and female rats subjected to prenatal stress on the model of swimming in cold water (10°C, 5 min, days 10-16 of gestation) were studied. Prenatal stress had no significant effects on the blood levels of IL-6 and IL-10 cytokines. The blood concentration of proinflammatory cytokine TNFα in 60-day-old rats was higher than in age-matched controls. Stress led to a lower level of anti-inflammatory IL-4 in the blood of 30-day-old males compared to controls. In female rats subjected to prenatal stress, the concentration of IL-4 decreased on day 21, but increased by day 60 of postnatal ontogeny. Specific effects of prenatal stress on the blood cytokine profile in male and female animals at different periods of ontogeny were revealed. Different and even opposite changes in blood cytokine levels could be largely mediated by sex- and age-specific features of immune functions after prenatal stress.

Behavior of In Utero Stressed Rats in the Elevated Plus Maze Test during Different Periods of Postnatal Ontogeny.

We studied the effect of prenatal stress (dams were forced to swim in cold water (10°C; 5 min) from day 10 to 16 of gestation) on the behavioral parameters of the offspring in an elevated plus maze on days 21, 30, and 60 of life (suckling, infantile, and juvenile ages, respectively). Females at the suckling age demonstrated suppressed orientation and exploratory activity and increased anxiety, which returned to normal by the infantile and juvenile periods. Prenatally stressed males in juvenile age were characterized by reduced anxiety (assessed by the time spent in the closed and open arms of the plus maze). Thus, the effect of prenatal stress on the behavioral parameters manifested differently depending on the sex and stage of postnatal ontogeny. The modulatory effects of prenatal stress on the analyzed behavioral parameters were more pronounced in females at early stages of postnatal ontogeny (suckling and infantile ages).

Bone Marrow Multipotent Mesenchymal Stromal Cells from Patients with Aplastic Anemia Retain Their Ability to Support Hematopoietic Precursors despite Pronounced Changes in Gene Expression.

The properties of bone marrow-derived multipotent mesenchymal stromal cells (MSC) of patients with aplastic anemia at the onset of the disease are studied insufficiently. The aim of this work was to test the ability of MSC from patients with aplastic anemia to maintain hematopoietic precursors and to analyze the expression of genes associated with hematopoiesis and immune response. The ability of MSC to maintain hematopoietic precursors was determined by counting cobblestone area-forming cells; gene expression was analyzed by quantitative PCR. It was shown that MSC of patients with aplastic anemia preserve their ability to maintain hematopoietic precursors. Pronounced changes in the expression of the VEGFA and ANGPT1 genes were found. MSC from aplastic anemia patients with PNH clone significantly differ from those from aplastic anemia patients without PNH clone in terms of the expression of the SDF1, IL1R, and VEGFA genes. Changes in gene expression can be associated with the pathogenesis of the disease.

Effect of Repeated Stress Exposures on the Blood Cytokine Profile in Rats with Different Behavioral Parameters.

Changes in the blood cytokine profile were studied in rats with different behavioral patterns in the open-field test during chronic stress on the model of daily 4-h immobilization over 8 days. The level of proinflammatory cytokines IL-1α and IFNγ in behaviorally active and passive animals changed insignificantly under these experimental conditions. Repeated stress exposures were accompanied by a progressive decrease in the plasma level of IL-2 and IL-5 in passive rats; these changes were most pronounced on day 8 of the study. Active animals were characterized by a tendency toward reduction of IL-2 content, but significant decrease in IL-5 concentration on days 3 and 8 of restraint stress. Blood levels of IL-1ß and IL-6 in rats remained practically unchanged after single immobilization, but progressively increased during further stress exposures and reached maximum on day 8 of stress. The content of the anti-inflammatory cytokine IL-4 in rats was constant, but blood concentration of IL-10 increased during repeated stress exposures. These changes were most pronounced on day 8 in passive animals and on days 3 and 8 of restraint stress in active animals. These data indicate that the direction of variations in the blood cytokine profile of rats under conditions of chronic stress depends on the baseline parameters of behavior and frequency of stress exposures.

IGAxBSA composite for assessing disease severity and response in patients with atopic dermatitis.

BACKGROUND: Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time-consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD. OBJECTIVE: To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness. METHODS: The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate-to-severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014-001198-15), LIBERTY AD SOLO 2 (NCT02277769, 2014-002619-40), LIBERTY AD SOLO-CONTINUE (NCT02395133, 2014-003384-38), LIBERTY AD CHRONOS (NCT02260986, 2013-003254-24), LIBERTY AD CAFÉ (NCT02755649, 2015-002653-35), LIBERTY AD ADOL (NCT03054428, 2015-004458-16), LIBERTY AD PEDS (NCT03345914, 2016-004997-16), LIBERTY AD OLE (NCT01949311, 2013-001449-15) and LIBERTY AD PEDS OLE (NCT02612454, 2015-001396-40). RESULTS: Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open-label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient- or caregiver-reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P < 0·0001), and concordance between IGAxBSA-50/75/90 and EASI-50/75/90 was excellent (88-94%). CONCLUSIONS: IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race.

Lymphocyte Index of Peripheral Blood in Rats at Different Stages of the Post-Stress Period under Conditions of Antigenic Exposure and Injection of Lipopolysaccharide.

Changes in the Shaganin lymphocyte index (ratio of the number of lymphocytes to segmented neutrophils) in the peripheral blood of rats after intraperitoneal administration of LPS (100 µg/kg) at the end of a single stress exposure in a model of 24-h restraint stress were studied. The lymphocyte index was analyzed 3 h later, on the 1st and 8th days after the stress load. Immobilization was accompanied by a decrease in this parameter 3 h after exposure. One day after the stress load, an increase in the lymphocyte index was noted, which remained on the 8th day of observation. LPS injection did not affect the changes in this parameter caused by 24-h immobilization on the 1st and 8th days of the study, but prevented a pronounced increase in the lymphocyte index on the 1st day after the stress load. The data obtained expand the existing scientific understanding of the specificity of the involvement of immunomodulatory substances in the implementation of adaptive-compensatory processes in mammals under conditions of emotional stress.

Correlation of Physiological Parameters in Rats after Stress Exposure under Conditions of Antigenic Stimulation with Lipopolysaccharide Administration.

We studied correlation dependences between physiological parameters in rats in 3 h, 1 day, and 8 days after administration of LPS (100 µg/kg) at the end of 24-h immobilization stress. In 3 h after LPS administration against the background of stress exposure, significant correlations of metabolic parameters with the relative weight of the adrenal glands and the perceptual component of nociception in rats were revealed. A direct relationship between the concentration of the proinflammatory cytokine TNFα and anti-inflammatory IL-4 was also found in these animals. On the first day after LPS injection, correlations were revealed, predominantly positive, only between the indicators of the cytokine blood profile. In the late post-stress period after antigenic exposure, no correlations between the studied physiological parameters were found. It can be hypothesized that immune modulation through systemic administration of LPS prevents persistent excessive stress of physiological functions at the later stages after stress exposure.

[Monoclonal antibody therapies for rapidly progressive and highly active multiple sclerosis in the era of the COVID-19 pandemic]. / Terapiya monoklonal'nymi antitelami bystroprogressiruyushchego i vysokoaktivnogo rasseyannogo skleroza v epokhu pandemii COVID-19.

As the COVID-19 pandemic continues, reducing the risk of infection for immunocompromised patients remains an important issue. Patients with aggressive multiple sclerosis (MS) require immunosuppressive therapy in order to control the overactive autoimmune response. Preliminary international and national trials demonstrate that older age, higher disability status and progressive MS are generally associated with a more severe clinical course of COVID-19. However, uncertainty remains about the effect of disease-modifying therapies on the COVID-19 clinical presentation. In this article, we pay special attention to monoclonal antibodies used for immune reconstitution therapy, which results in significant changes to the T-cell and/or B-cell repertoire. Based on the published data from registries in different countries, we attempted to estimate the benefits and risks of these therapies in a complicated epidemiological setting.

Spike Activity in the Ventromedial Nucleus of Rat Hypothalamus during Aging.

Spike activity of neurons in the ventromedial nucleus (VMN) of the hypothalamus in adult (6-8 months) and aged (2 years) male rats was studied by the in vivo extracellular method using stereotaxic insertion of microelectrodes. In all animals, firing frequency of most VMN neurons increased in response to glucose administration. However, in aged rats, the mean baseline and glucose-induced spike frequencies of VMN neurons were lower than in adult animals. These results support the hypothesis that aging is associated with a decrease in the functional activity of hypothalamic neurons.

[Immunosupressive therapy of aplastic anemia patients: successes and failures (single center experiment 2007-2016)].

Treatment programs for patients with acquired aplastic anemia include two main therapeutic options: allogeneic bone marrow transplantation and combined immunosuppressive therapy (IST). However, combined IST remains the method of choice for most adult AA patients. This study included 120 AA patients who received IST at the National Research Center for Hematology in 20072016. The analysis was applied to 120 patients. Median age was 25 (1765) years, M/F: 66/54, SAA/NSAA: 66%/34%. Effectiveness of IST was carried out in 120 patients with AA. This group did not include 8 SAA patients who died during the first 3 months from the start of treatment from severe infectious complications (early deaths 6.2%) and 2 AA patients who dropped out of surveillance. The observation time was 55 (6120) months. Paroxysmal nocturnal hemoglobinuria (PNH clone) was detected in 67% of AA patients. The median PNH clone size (granulocytes) was 2.5 (0.0199.5)%. The treatment was according to the classical protocol of combined IST: horse antithymocytic globulin and cyclosporin A. Most of patients (87%) responded to combined immunosuppressive therapy. To achieve a positive response, it was sufficient to conduct one course of ATG to 64% of patients, two courses of ATG 24% of patients and 2% of patients responded only after the third course of ATG. A positive response after the first course was obtained in 64% of patients included in the analysis. Most of the responding patients (93%) achieve a positive response after 36 months from the start of treatment. Therefore, the 3rd6th months after the first course of ATG in the absence of an answer to the first line of therapy can be considered the optimal time for the second course of ATG. This tactic allows to get an answer in another 58% of patients who did not respond to the first course of ATG. The probability of an overall 10-year survival rate was 90% (95% confidence interval 83.696.2).

[Experience in designing an electronic multiple sclerosis registry]. / Opyt sozdaniya elektronnogo registra patsientov s rasseyannym sklerozom.

OBJECTIVE: To develop an electronic registry of patients with MS in the Russian Federation and to analyze the collected epidemiological and clinical data. MATERIALS AND METHODS: Patients aged 18 and older with definite multiple sclerosis were included in the study. We designed a specialized electronic individual registration form (registry) to gather information about study participants. This paper presents data collected in the project between September 25, 2017 and March 25, 2020. RESULTS: We collected information on 2728 patients. This paper presents the results of data analysis from the registry of MS patients, including demographic, clinical and epidemiological characteristics, the type and timing of treatment received. Based on the data obtained, certain issues with primary diagnosis of multiple sclerosis and delayed initiation of disease-modifying therapy can be highlighted, which contribute to the transition of the disease to a secondary progressive course and disability increase.

Blood Cytokine Concentration in Rats during Antigenic Treatment after a Single Long-Term Stress Exposure.

We studied changes in the blood cytokine profile of rats 3 h, 1 day, and 8 days after acute stress on the model of 24-h immobilization followed by LPS administration (100 µg/kg intraperitoneally). The concentration of proinflammatory cytokines (particularly of IL-1ß and TNFα) significantly decreased at the early stage after stress exposure and physiological saline injection, but increased in the follow-up period and practically did not differ or even surpassed the control level by the end of observations. Under these conditions, the blood content of anti-inflammatory cytokine IL-10 increased most significantly on day 1 of the post-stress period. Restraint stress followed by LPS administration was accompanied by a decrease in the level of proinflammatory cytokines at the early (IFNγ and TNFα) and late stages (IL-1ß) of the experiment. Directed modulation of the immune status in animals after acute stress was followed by a significant increase in the content of IL-10 on days 1 and 8, as well as by a tendency toward elevation of IL-4 concentration by the end of the study. The directionality and degree of changes in the cytokine profile of mammalian tissues depend on the type of extreme exposure, duration of the post-stress period, and specific effects of exogenous pathogenic factors in the whole body.

State of Stress-Marker Organs in Rats after a Single Exposure to Long-Term Stress and Treatment with Lipopolysaccharide.

We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 µg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.

Blood Cytokine Profile in Rats with Different Behavioral Characteristics after Metabolic Stress.

Changes in the blood cytokine profile in rats with various parameters of behavior were studied under conditions of 5-day starvation not followed by the recovery period or with subsequent normalization of food intake. Metabolic stress had no effect on the content of most cytokines. The concentration of pro- and anti-inflammatory cytokines in blood plasma of rats was shown to increase significantly by the end of a 5-day recovery period after food deprivation. These changes in behaviorally passive specimens were more pronounced than in active animals. Therefore, differences in the strain of immune reactions in mammals with different prognostic resistance to extreme factors are most pronounced during the post-stress period. These data illustrate the necessity of an individual approach to studying the systemic organization of physiological functions under normal and pathological conditions.

[Leptomeningeal B-cell follicles in multiple sclerosis: a role in the pathogenesis and prognostic value]. / Éktopicheskie limfoidnye V-kletochnye follikuly pri rasseiannom skleroze: rol' v patogeneze zabolevaniia i prognosticheskaia znachimost'.

B-lymphocytes play an important role in the development and maintenance of the inflammatory process in multiple sclerosis. Recently special attention has been paid to cell formations that are found in the meninges in patients with multiple sclerosis - the so-called leptomeningeal follicle-like structures that contain not only B-lymphocytes, but also other immunocompetent cells, creating a special environment for clonal expansion, selection and further proliferation of B-lymphocytes. Magnetic resonance imaging (MRI) of the brain with gadolinium-based contrast agents reveals local subarachnoid space contrasting that corresponds to the accumulation of the contrast agent by large lymphoid follicles. This phenomenon is called leptomeningeal contrast enhancement and according to some literature data, its severity correlates with the rate of progression of the disease and functional disability. The review presents the available literature on leptomeningeal follicle-like B-cell structures, as well as prospects of using leptomeningeal contrast enhancement on MRI as a potential biomarker for predicting disease severity in patients with multiple sclerosis.