bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in mononuclear cell subsets in capillary and venous blood of patients with psoriasis depending on the treatment
Authors: Sennikova S. V. , Toptygina A. P.
Published: October 2022

Topical glucocorticoids are conventionally used to treat psoriasis, but such treatment provides a short-term effect, and may cause various complications during long-term usage. A detailed study of the immunopathogenesis of psoriasis has made it possible to use bioengineered drugs that block the main cytokines. It has been shown that IL-36 plays an important regulatory role in pathogenesis of psoriasis. The aim of the study was to study therapeutic effect of patients with psoriasis using topical glucocorticoid hormone versus IL- 36 receptor antagonist (RAIL-36), with respect to clinical course of psoriasis and the subsets of mononuclear cells in venous and capillary blood taken close to the focus of inflammation. 16 patients with psoriasis (group 1a) received 0.1% mometasone cream for 14 days; 20 patients of group 1b received a gel containing 0.4% recombinant RAIL-36 for 14 days. Control group included 20 healthy adults. Treatment efficacy was assessed by PASI, DISHS and DLQI indices. 19 lymphocyte subsets and 3 monocyte subsets were assessed by four-color staining of whole capillary and venous blood with erythrocyte lysis using BD Biosciences (USA) technologies and reagents. It was shown that both drugs led to a decrease in the severity of the disease at the end of treatment. However, 2 weeks after the end of treatment in group 1a, the disease indexes nearly returned to the initial values. Meanwhile, the reduced index levels persisted 2 weeks later in group 1b. Significant deviations (more pronounced in capillary blood) were revealed for the levels of several leukocyte subsets in the psoriasis patients compared with healthy persons. As a result of treatment, we have revealed some changes in the levels of leukocyte subsets common to the two groups, and special differences for the two treatment options, that were more pronounced in capillary blood samples. Both medical preparations used are suitable for treatment of psoriasis.
Influence of ZP2 peptide, a synthetic analogue of the GM-GSF active center on the anticytokine activity of bacteria from Enterococcus genus and their ability to produce cytokine-like substances
Authors: Pashinina O. A. , Kartashova O. L. , Pashkova T. M. , Gritsenko V. A.
Published: October 2022

Peptide ZP2, a synthetic analogue of the active center of granulocyte-macrophage colony stimulating factor (GM-CSF), exhibits a wide range of immunobiological effects, including antibacterial activity. At the same time, its effect (in sub-inhibitory concentrations) on the biological properties of Enterococcus spp., the causative agents of many infectious and inflammatory diseases remains poorly understood. The aim of our study was to analyze the nature of the effect of synthetic peptide ZP2 on anticytokine activity (ACA) and its ability to produce cytokine-like substances (CLS) in Enterococcus spp.

18 clinical isolates of Enterococcus spp. were used. Over the experiments, the bacterial strains were cultured in Schaedlers broth with ZP2 peptide at 37 C for 24 hours. No specific peptide was added in the control. ACA for IL-8, TNF and IL-17A and the production of the corresponding CLS were determined by the ELISA method. To assess ACA, the proportion of cytokine inactivation in the experiment relative to the control was calculated and expressed in pg/ml; CLS production was evaluated by the level of cytokines in the experiment and control, expressed as pg/ml. The data were subjected to statistical processing.

It was revealed that Enterococcus spp. strains are capable of secreting compounds that inactivate cytokines IL-8, IL-17A and TNF, and produce CLS in the culture medium. Intragenital and intraspecific variability was noted in the presence and frequency of occurrence and in the severity of these properties. It was found that the ZP2 peptide in E. faecium increases ACA with respect to all studied cytokines. When tested with E. faecalis, it either did not affect their ACA against TNF and IL-8, or completely inhibited ACA for IL-17A. At the same time, ZP2 blocked the production of CLS, e.g., IL-17A and IL-8 in E. faecium, but increased the production of CLS similar to TNF, and, with E. faecalis, it increased the number of IL-17A-producing isolates twofold, although the average level of production of these CLS was lower than in the control.

Enterococcus spp strains are capable of secreting compounds that inactivate cytokines IL-8, TNF and IL- 17A, and may produce substances similar to these cytokines. The synthetic peptide ZP2 has a modifying effect on the manifestation of these properties by Enterococci. Further studies of biological and pathogenetic features of Enterococci and other bacterial species, as well as modifying effects of the ZP2 peptide are required.
Dynamics of immune system parameters in development of SARS-CoV-2-specific immunity in a patient with common variable immune deficiency
Authors: Sizyakina L. P. , Andreeva I. I. , Kharitonova M. V.
Published: October 2022

With the accumulation of data on the evolving SARS-CoV-2 infection pandemic, it became clear that the risk factors for severe course of COVID-19 among the patients with primary immunodeficiency include disorders associated with dysregulation of the immune response. In this regard, it is of interest to identify possible predictors of the pronounced inflammatory reaction upon infection with coronavirus in the patients with general variable immune insufficiency. For this purpose, the dynamics of immune system parameters was studied in a patient with CVID who underwent a severe clinical variant of COVID-19, as an example of clinical case.

We present patient K., 49 years old, with CVID diagnosis verified at the age of 35 years who received regular replacement therapy with IVIG. He suffered from COVID-19 in severe form, received anti-cytokine therapy and an additional course of IVIG during the treatment. He was discharged in satisfactory condition. The quantitative and functional parameters of the T and B lineages of immune system were evaluated by flow cytofluorimetry during routine examinations before the infection and three months after the discharge from the hospital after COVID-19. It has been shown that, before the disease, there were changes in the parameters of B cells characteristic of CVID manifesting as a decrease in switched-memory B cells and plasmoblasts. Alterations in the T cell subsets were also revealed, as redistribution of the subpopulation composition towards T effectors with an increased cytolytic potential of these cells and a weakening of T cell suppression, due to decreased Treg in peripheral blood. After undergoing COVID-19, the patient developed specific IgM and IgG antibodies. The development of immune response was accompanied by an increase in the number of un-switched and switched memory B cells. At the same time, we have registered an increase in memory T cells ready for the proliferative response of T helper cells and Treg cells. The initial pro-inflammatory pattern of the T cell lineage system in our patient with CVID is explained by the implementation of the compensatory capabilities of the immune system, thus leading to activation of the cytolytic effects of cellular compartment in adaptive immune response, along with attenuation of the humoral component. Moreover, it is likely that these changes contributed to the clinical course of COVID-19 in this clinical case. Development of a specific humoral response to SARS-CoV-2 in a patient with CVID after a COVID-19 infection is accompanied by an increased proportion of memory B cells, coordinated dynamics of T cell suppression and activation parameters.
Association of the cytokine profile and metabolic syndrome components in young patients
Authors: Sumerkina V. A. , Telesheva L. F. , Golovneva E. S.
Published: October 2022

The components of metabolic syndrome (MS) are independent factors of cardiometabolic risk and are associated with impaired humoral immunity. However, the literature data on the cytokine profile features in MS are ambiguous. Therefore, associations between cytokine levels and MS components were determined in a group of MS patients of both sexes, as well as indices of visceral adipose tissue function were studied. The work included 149 patients aged 18-45 years. The patients were divided into 2 groups: group 1 (n = 71) included patients without abdominal obesity and MS components (comparison group); group 2 (n = 78), patients with MS. The concentrations of glucose, glycosylated hemoglobin, insulin, total cholesterol, HDL-C, LDL-C, triglycerides, leptin, adiponectin were determined. The indexes of insulin resistance HOMA-IR, Tg/HDL and TyG, as well as marker of visceral adipose tissue dysfunction VAI were calculated. ELISA technique was used to determine the concentration of IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IFN, IFN, МСР-1 и TNF. Results: In the patients with MS, we have found increased levels of IL-6, IL-10, MCP-1, and decrease of IL-2, IL-4, IFN levels. Correlation analysis established a relationship between glucose levels and MCP-1; glycosylated hemoglobin and IL-6, TNF. Among the indices of lipid metabolism, we have revealed some associations between LDL-C and IFN; HDL-C and IL-2, IL-4, IFN. The levels of triglycerides correlated with MCP-1. A negative relationship between the presence of arterial hypertension and the IL-4 contents was established. A negative correlation of leptin levels with IL-4 and IFN concentrations was also determined. Markers of insulin resistance (Tg/HDL and TyG) were associated with MCP-1 chemokine, thus supporting chronic inflammatory process. The VAI index, which reflects the dysfunction of visceral adipose tissue, showed a correlation with MCP-1. Thus, the results of investigation suggest an involvement of the cytokine system in the disorders of visceral adipose tissue and development of the metabolic syndrome.
Complicated ways of diagnosing common variable immune deficiency (case report)
Authors: Moskalets O. V.
Published: October 2022

Common variable immunodeficiency (CVID) is one of the most frequent forms of primary immunodeficiencies with predominant antibody deficiency. Unlike most other primary immunodeficiencies, this variant often manifests in adults thus creating certain difficulties in its detection. Manifestations of common variable immune deficiency are very diverse: infectious syndrome (respiratory tract infections, septic arthritis), diarrheal clinical pattern of both infectious and non-infectious genesis, autoimmune syndrome (autoimmune cytopenias, systemic rheumatic diseases), lymphoproliferative syndrome (benign lymphoid proliferation, lymphomas), interstitial lung disease and sarcoidosis-like granulomatous changes are quite common. Due to the lack of a distinct clinical pattern, the common variable immunodeficiency is often diagnosed too late. Such patients are observed for a long time by various specialists, and the absence of pathogenetic therapy (intravenous immunoglobulins) leads to steady progression of the disease and, often, to lethal outcome. The article presents a clinical observation illustrating the difficulties in making this diagnosis. A woman hospitalized with pneumonia presented with a mass in colonic submucosa. After excluding tuberculosis and lymphoma, a diagnosis of colon lipoma was made on the basis of histological examination. A few years later, the patients submandibular lymph nodes were periodically enlarged. Upon repeated histological examination, the diagnosis of granulomatous necrotizing lymphadenitis was established, the patient was referred to a rheumatologist to rule out systemic vasculitis. This diagnosis was not confirmed, but further examination revealed a sharp decrease in the gamma fraction of serum proteins. Therefore, an immunologists counseling was recommended to rule out immunodeficiency. The following blood serum analysis revealed an extremely low IgG and IgM content, with absence of detectable immunoglobulin A. On the basis of these findings, the diagnosis of common variable immune deficiency was made for the first time. Replacement therapy with high-dose intravenous immunoglobulins with control of pre-transfusion Ig levels was recommended, with further transition to a supporting treatment schedule. Hence, one may state that general practitioners are still poorly aware of primary immunodeficiencies, especially if non-infectious manifestations dominating in the clinical pattern. Routine analysis of total protein content and protein fractions can provide information that allows to suspect deficiency of antibodies and, therefore, to assess contents of distinct serum immunoglobulins in order to confirm CVID diagnosis.
Relationships between the factors of innate immune system and results of neurocognitive function parameters in the persons living with HIV infection: interim results of the study
Authors: Knysh S. V. , Sklyar L. F. , Cherkasova Yu. S. , Chernikova A. A. , Knysh A. A. , Nevezhkina Tatiana A. , Chagina E. A.
Published: October 2022

HIV infection is closely associated with damage to the nervous system, even despite usage of antiretroviral therapy. Thus, the patients are at a high risk for neurological complications. Due to limited permeability of the blood-brain barrier, the opportunity of its damage, both directly by the proteins of HIV-infected cells and indirectly, by immune system, e.g., inducing the production of inflammatory mediators, the involvement of the central nervous system in pathogenesis of HIV infection seems to be only a matter of time. HIV-associated neurocognitive disorders (HAND) comprise a poly-etiological pathological condition associated with direct and indirect damage to neurons in HIV infection. The role of interaction between the innate immune system and nervous system mediators in viral infections suggests that the specific changes in content and ratios of pro- and anti-inflammatory cytokines that are among the most polypotent mediators of immune regulation can be detectable in the persons prone to the development of HAND in HIV infection. The purpose of the present study was to characterize the features of serum content and the relationship between the indexes of innate immunity factors with the results of neurocognitive testing in the persons living with HIV.

123 persons were included in the study, of which 93 subjects live with HIV infection. They were divided into 3 groups according to the stages of HIV infection, according to the Russian Classification of HIV infection. 30 persons represented a group of healthy volunteers, comparable in age and gender with the members of main groups, and served as a control group. Determination of IL-1 and IL-10 contents in blood serum was carried out by solid-phase enzyme immunoassay. The level of CD4+T lymphocytes was determined by flow cytometry. Neurocognitive testing using Schulte tables, the Munsterberg test was conducted by a medical psychologist, according to generally accepted methods.

A significant increase in the serum IL-10 content in subjects from the main groups was revealed as compared with the control group, as well as in group III compared with the values groups I and II. The levels of IL- 1, CD4+T lymphocytes were significantly lower in group III, compared with all other groups. The personal performance index determined by testing with Schulte tables was reduced in all groups, relative to the controls, with a significant predominance of the results in groups I and II over the results of the participants from group III. The scores in Munsterberg test were equally diminished in all the main groups compared to the control values. When assessing the Spearman coefficient, the presence of various correlation profiles was established, depending on the stage of the disease.
Dynamics of cell-free DNA levels in the in vivo LPS-induced inflammation model
Authors: Demchenko E. N. , Gavrilova E. D. , Goiman E. V. , Volskiy N. N. , Kozlov V. A.
Published: October 2022

An increased concentration of extracellular cell free DNA (cfDNA) is a distinctive characteristic of pathologies that mainly occur in acute inflammation (myocardial infarction, sepsis, stroke, trauma). The increase of cfDNA in chronic inflammatory processes, oncological, autoimmune diseases is less significant and is mainly due to aberrant cell death processes. One of such diseases is systemic lupus erythematosus (SLE). It has recently been shown that, in addition to increased cfDNA concentration, the degree of inflammation can reflect the N/L index (neutrophil to lymphocyte ratio), being a simple and informative marker of disease activity in patients with SLE. The aim of the study was to study the dynamics of the level of cfDNA and the N/L index in the model of LPS-induced inflammatory response as observed in intact mice, and their relation to the phenotypic heterogeneity of model SLE. We used female hybrid mice (C57Bl/6xDBA/2) F1 and female DBA/2 mice at the age of 6-8 weeks. LPS of E. coli strain 111: B4 (Sigma) was injected intraperitoneally once at doses of 10 ng, 1 g and 100 g per mouse in PBS. The control group was injected with the appropriate volume of buffer. The TNF-binding domain of the variola virus CRMB protein was used as an inhibitor of TNF, which was administered 30 min before the introduction of LPS. The dynamics of the response to LPS was assessed after 4, 8, 11, 24 hours by the N/L index and the level of cfDNA; at the zero point, the parameters were determined before the introduction of LPS. A day after a single injection of LPS at a dose of 1 g/mouse, a SLE model was induced on the same hybrid mice (double intravenous administration with an interval of 6 days of spleen cells of the DBA/2 line, 60-70 106 cells each). Three months later, with proteinuria of 3 mg/ mL or more, mice were assigned to the SLEnephritis+ group, with a protein of less than 3 mg/mL, to the SLEnephritis- group. Statistical processing of the results was carried out by nonparametric statistics using the MannWhitney test. Differences were considered statistically significant at p 0.05. It was found that the change in the N/L index, as well as the change in the level of cfDNA, depends on the dose of LPS administered. It was shown that the level of cfDNA reaches its maximum after 8 and 11 hours after the introduction of LPS is reliably reduced when using the inhibitor TNF. A retrospective analysis indicates that there is a definite relationship between the response of intact mice to LPS before induction of cGVHD, and their subsequent division into variants of SLEnephritis + and SLEnephritis - in the course of disease development.
Features of humoral immunity in patients with mild traumatic brain injury
Authors: Norka Anna O. , Vorobyev S. V. , Kuznetsova R. N. , Serebriakova M. K. , Kudryavtsev I. V. , Kovalenko S. N. , Monashenko D. N. , Korobova Z. R.
Published: October 2022

Traumatic brain injury (TBI) is an important problem of the healthcare system. A lPeading role in pathogenesis belongs to the action of shock wave upon skull and brain integuments, extending from the impacted site, as well as displacement and rotation of the cerebral hemispheres relative to the fixed brain stem. As a result, a cascade of metabolic, biochemical and inflammatory changes is initiated, leading to secondary damage. TBI, depending on its mechanism, severity and type, causes various primary structural and functional brain lesions at molecular, cellular, tissue and organ levels with dysregulation of all systems in the body, dependent on its degree and extent. In most cases, the brain injury increases the risk of developing epilepsy and neurodegenerative diseases such as Alzheimers disease, arkinsons disease and chronic traumatic encephalopathy (CTE), with mental health disorders. TBI is a long-term symptomatic process in patients with functional and structural damage. In response to a traumatic event, the damage-associated molecular patterns (DAMPs) encountered upon tissue damage are expressed, which cause activation of the resident brain tissue cells, and secretion of multiple chemokine and cytokine by distinct cell populations. Neutrophils migrate to focal lesions, which remove damaged cells and debris. Migration of T and B cells is observed 3-7 days after the trauma. Hence, following primary injury, due to a cascade of immune reactions, a more extensive lesion, the so-called secondary trauma, is developed. The aim of our study was to evaluate the role of immune response in pathogenesis of mild traumatic brain injury.

An increased number of Bm2 cells, IgDdimCD27low naive B cells and B cells with the IgDlowCD27hi (plasmablasts) phenotype was found in patients with mild brain contusion, compared to comparison group. Moreover, the number of naive mature B cells with the CD27lowCD38dim phenotype was significantly decreased compared with the controls.
Phenotypic features of innate lymphoid cells in rheumatoid arthritis
Authors: Boeva O. S. , Berishvili M. T. , Sizikov A. E. , Pashkina E. A.
Published: October 2022

Currently, rheumatoid arthritis (RA) is considered among the most common autoimmune diseases worldwide, being associated with progressing disability, systemic organ and tissue lesions, as well as social and economic losses for the state. Studies of innate lymphoid cells (ILS) seems to be actual and significant when studying development of autoimmune inflammation in RA, in particular, the issues of the cell plasticity. ILC represent tissue resident lymphoid cells that display functional diversity, like as T cells. Moreover, ILC regulate orientation of immune response by means of cytokine production. Small amounts of ILCs are present in the bloodstream, presumably for migration to target organs and tissues. Accordingly, the study of ILC in RA will promote understanding of the RA pathogenesis. It is also possible in the future to develop new therapeutic strategies based on the impact on the immunological balance, as well as reducing the inflammatory process in RA. The aim of this study was to determine the subpopulation composition and phenotypic features of ILCs in RA.

We have isolated and studied peripheral blood mononuclear cells (PBMC) from 7 patients with RA and 6 healthy donors. The isolated blood MNCs were stained with monoclonal antibodies conjugated to fluorochromes: lineage-specific (CD3/14/16/19/20/56) and anti-FceR1 alpha-FITC, anti-CD294-APC/Cy7, anti-CD127-PerCP/Cy5.5, anti-CD336-PE, anti-CD117-APC. ILCs were defined as Lin-CD127+. The numbers of CD294+ILCs (ILC2) were estimated in the general population, CD117-CD294-ILCs were defined as ILC1, and CD117+CD294-ILCs, as ILC3. The cell phenotype was analyzed with a FACS Canto II flow cytometer (BD Biosciences, USA).

We determined relative numbers of different ILC subpopulations (ILC1, ILC2, and ILC3) among the total blood MNCs. It was shown, that the number of ILC2 cells in RA patients was statistically significantly reduced compared to healthy donors, whereas no significant differences in percentage of ILC1 and ILC3 were revealed between donors and patients. We also evaluated the amount of c-Kit+ILC2; there were no significant differences in the proportion of these cells between donors and patients.

ILCs represent a population of cells that contribute to the RA pathogenesis. The role of ILC2 in RA is, presumably, protective. The ILC imbalance may contribute to the development of RA. For a better understanding of the RA pathogenesis, further studies of the subpopulation profile, phenotypic and functional characteristics of ILC are required in this disorder.
Role of innate errors of immunity in the group of children with fatal outcomes during the first year of life
Authors: Cheremokhin D. A. , Tuzankina I. A. , Chereshnev V. A. , Bolkov M. A. , Shinvari Kh.
Published: October 2022

In the modern world, inborn errors of immunity (IEIs), or primary immunodeficiencies (PIDs), are among of the main causes of childhood disability and mortality, determining the demographic state of mankind not only at present, but also in the future. In the Sverdlovsk Region over the past 5 years, there were about 30% of children who died from severe combined primary immunodeficiency. This retrospective study is devoted to the study of the nosological profile of mortality in the children with immune-dependent disorders in the Sverdlovsk Region, as well as to assess information significance of extrachromosomal circular DNA molecules (TREC and KREC) analysis. Some anamnestic data on the course of prenatal period in the current and previous pregnancies were considered the signs of suggested diagnosis of primary immunodeficiencies, i.e., threats of pregnancy loss at the early terms, documented cases of early childhood death, persistent viral and bacterial infections in the mother, complicated course of pregnancy in the mother, as well as some clinical manifestations, including fungal-bacterial sepsis, generalized viral infection, repair disorders, reduced physiological tolerance accompanied by autoimmune organ damage and uncontrolled systemic inflammation. The study demonstrated a wide range of nosological entities of innate errors of immunity in the structure of early childhood mortality, including both classical forms of primary immunodeficiencies and the disorders not directly related to innate errors of immunity, but those showing phenotypically pronounced immunodeficiency and their immediate role in statistical deviations. Among the main criteria that may presume possible presence of an immune-dependent pathology in the early neonatal period we considered the molecular markers of naive T and B cells (TREC and KREC, respectively) revealed in 70% of the cases studied, with, at least, one of these indexes found to be reduced. It is important to understand that primary immunodeficiencies are not as rare as previously thought. Therefore, it is necessary to carry out timely and high-quality diagnostics, in order to avoid unavoidable deaths.
Mucosal immunity during rehabilitation in the patients after coronavirus infection
Authors: Khasanova A. А. , Kostinov M. P. , Soloveva I. L.
Published: October 2022

Following the coronavirus infection, a variety of symptoms may persist for a long time. Therefore, an important area of further research is to study the state and response of protective immune mechanisms in the post-COVID period. Our aim was to evaluate the dynamics of mucosal immunity by measuring sIgA in the saliva samples and nasal swabs (sIgA, lactoferrin), as well as efficiency of interferon-alpha-2b (IFNa2b) treatment in the patients after coronavirus infection.

A study was conducted in the patients aged 18 to 60 years (n = 130) at the terms of 1 to 9 months after a coronavirus infection. A control group consisted of conditionally healthy individuals (n = 15). Diagnosis of post-COVID manifestations was carried out by collecting complaints, anamnestic data, physical examination and questionnaire. The state of mucosal immunity in saliva samples and nasopharyngeal mucosal scrapings was evaluated in dynamics as based on determination of sIgA and lactoferrin concentrations by means of enzyme immunoassay techniques prior to administration of local preventive therapy with recombinant IFNa2b, and 1 month after the treatment (VIFERON gel applied intranasally twice a day for 30 days).

The following symptoms of post-COVID syndrome were documented In the study group: joint and muscular pain, shortness of breath, cough, fatigue and weakness, headache and dizziness, anxiety. In the group of patients who received preventive therapy during 1 to 3 months after coronavirus infection, a significantly increased level of saliva sIgA was noted, respectively, 1.840.28 to 5.781.96 mg/mL. As based on the data obtained with scrapings from nasopharyngeal mucosa, a significant increase in the level of sIgA was revealed in the group subjected to therapy up to 3 months after COVID-19 infection, i.e., from 28.613.0 to 39.833.85 mg/mL. In the group of patients devoid of preventive therapy, a stable maintenance of the reduced mucosal immunity parameters was found in all time intervals during the period of convalescence. In all observed patients, regardless of the group, a decreased lactoferrin level was found, being two-fold lower than the normal reference values. The incidence of respiratory viral infections in the group without preventive therapy was statistically significant, being registered in 9.2% of cases.

Patients after COVID-19 infection exhibit a persistent decrease in mucosal immunity. Immunological efficacy was observed when using IFNa2b, thus making it possible to recommend it for rehabilitation in this group of patients over the period of convalescence.
HBD1 and LL37 gene expression in children with atopic dermatitis
Authors: Bystritskaya E. P. , Murashkin N. N. , Materikin Alexander I. , Naumova E. A. , Yakovleva I. V. , Vartanova N. O. , Svitich Oxana A.
Published: October 2022

Atopic dermatitis (AD) is a multifactorial genetically determined inflammatory skin disease characterized by itching, chronic course, age-related features of localization and lesion morphology. Atopic dermatitis is caused by complex interactions between genetic, immunological, and environmental factors. The barrier function of the skin is impaired in atopic dermatitis. Antimicrobial peptides, e.g., LL-37, b-defensins are involved in maintaining the skin barrier function (especially, intercellular contacts). An imbalance of antimicrobial peptides may cause different disorders, including allergic pathologies. The aim of this study is to investigate gene expression profile of the HBD1 and LL37 encoding antimicrobial peptides in the samples of skin and blood mononuclear cells obtained from the children with moderate and severe atopic dermatitis before and after treatment. By means of real-time polymerase chain reaction, the levels of HBD1 and LL37 gene expression were evaluated in the samples. Statistical analysis showed significantly increased (p 0.017) expression levels of both HBD1 (H-test = 24.76; 2, n = 72; p = 0.00001), and LL37 genes (H-test = 15.69; 2, n = 72; p = 0.00039) in blood cells of AD patients compared to the control group, as well as decreased (p 0.05) levels of HBD1 expression in the affected skin compared to the control group. Our data on the cathelicidin gene in the skin do not differ from the literature data, since its expression is reduced in AD. In our series, an increase of the gene expression was revealed in PBMCs. The HBD1 peptide is expressed in both monocytes and macrophages, representing a link between innate and adaptive immunity. In our study, the expression of the HBD1 gene was increased only in blood, thus suggesting activation of innate immunity components at the systemic level in response to inflammation. Of importance, understanding the role of immunological markers in AD will help to develop novel prognostic approaches in management of the patients with atopic disorders. Therefore, one should understand pathogenetic mechanisms of allergic diseases.
Increase of blood neuregulin 4 is associated with type 2 diabetes mellitus and hypertension in obese patients
Authors: Vulf M. A. , Safiullina L. A. , Gazatova N. D. , Kuznetsov G. L. , Komar A. A. , Kirienkova E. V. , Litvinova L. S.
Published: October 2022

Obesity and type 2 diabetes mellitus (T2DM) are global epidemics at the present time, being a serious public health issue. An increased prevalence in the number of obese people promotes a risk for developing cardiovascular diseases (CVD) and some types of cancer. The ErbB signaling pathway plays a significant role in development of the disorders associated with metabolic dysfunction (e.g., T2DM, obesity, arterial hypertension). Neuregulin 4 (NRG4) is a new adipokine with similar effects to adiponectin. Interaction between the ErbB3, ErbB4 receptors and their ligand, NRG4, launches the processes required to maintain the energy balance in the cells. There are controversial literature data on NRG4 levels in blood circulation. In particular, the existing data concerning functions / mechanism of NRG4 action has been obtained in experimental animals and cell lines, which is not always reproducible in humans. According to some works, liver may be the key target organ for NRG4. The present article is devoted to assessment of relationships between the NRG4 level in blood, and the parameters of carbohydrate and lipid metabolism, as well as presence of diseases associated with obesity. The study included obese patients with and without type 2 diabetes. The content of NRG4, indices of carbohydrate and lipid metabolism in the blood was assessed by means of enzyme immunoassay and biochemical techniques, respectively. It was found that the level of NRG4 was increased in obese patients with T2DM compared with healthy donors, and obese patients without T2DM. Statistical evaluation by correlation and regression analysis revealed numerous relationships between NRG4 and the parameters of lipid and carbohydrate metabolism, as well as some correlations between the NRG4 levels and clinical disorders associated with obesity (type 2 diabetes and arterial hypertension). Thus, NRG4 may be involved into the development of dyslipidemia in obese patients. We consider an increase of blood NRG4 levels in obese patients with type 2 diabetes as a compensatory response to the increased insulin-mediated lipogenesis. The data obtained are important in search for new points of influence upon pathogenesis of diseases associated with metabolic disorders. Neuroregulin 4 and its receptors may be promising targets for the treatment of socially significant clinical disorders.
http://soar.usa.edu/scholprojects/98
Authors:   , Atkins Danny
Published: October 2022

Practice Problem: Since COVID-19, nurses have felt the pressure from the pandemic on their shoulders. The practice problem has helped nurses manage stressors to decrease the symptoms of burnout. PICOT: In critical care nurses (P), how does the implementation of HeartMath techniques for stress management (I) compared to standard practice (C) affect rates of absenteeism, request for assignment transfer, and resignations (O) over 8-weeks (T)? Evidence: The evidence that guided this project change is based on the Johns Hopkins nursing evidenced-based-practice model. Intervention: The intervention assisted critical care nurses in dealing with stress and fatigue by using HeartMath to support mindfulness to decrease burnout. Outcome: The available statistical evidence suggests that the measurement basis of the scales and subscales of the new POQA-R4 framework appears to be psychometrically sound and produced a significant positive change. Absenteeism, requests for transfers to other units, and resignations were all remarkably decreased. Conclusion: This DNP project has decreased the effects of stress by using HeartMath stress management in critical care nurses. The project was implemented and analyzed the findings to establish clinical significance and suitability.
Matrix Organization Analysis Using Grey Relational Analysis
Authors: TP Krishna Kumar , M Ramachandran , Chinnasamy Sathiyaraj , Mani Malarvizhi
Published: October 2022

Abstract. Conflict procedures used by task managers at Matrix via mission group engineers Described. Project that managers used a combination of procedures to make certain cooperation and war In companies, conflicts could have an effective impact and management can be effectively Determined. Conflicts have been seen as reactionary and the project supervisor mixed a combination of competitiveness and avoidance of warfare processes Management changed into observed to be useless whilst reliant. These effects are the area for war management concept provided information aid, which become tested and delicate with the aid of sizable laboratory research. Microscopic environments of organic cells Macromolecular meeting in vivo and the resulting exclusion quantity is dominated with the aid of effects. This function is diluted in vitro mobile way of life no. Here, the synthesis of the NM scale radius at the physiological stages of partial career Macromolecular meeting in vitro using macromolecular globules we have been provoked. We calculated the effect of the brought on crowd Immunocyto chemistry, thru nuclear microscopy (AFM) and AFM-enabled nano-indentation Extracellular and intracellular protein structure of human mesenchymal stem cells (MSCs). Extra-cellular Macromolecular meeting in tradition is directly brought on by using supramolecular meeting and cells the deposited extracellular matrix mediates the alignment of proteins, ensuing in Increases the alignment of intracellular act in cytoskeleton. The ensuing cell matrix Metallization similarly affected the adhesion, multiplication, and migration behavior of MSCs. In vivo and in vitro In vitro for MSCs and different cells, by increasing the reliability among products synthesized by cells. Very physiologically relevant in studies and gadgets Macromolecular meeting enables layout. Quote: Zeiger AS, Loe FC, Li R, Raghunath M, Van Vliet KJ (2012) Macromolecular Crowding
Feasibility study for in vitro analysis of infectious foodborne HEV
Authors: Semaan Dima , Scobie Linda
Published: October 2022

Hepatitis E virus (HEV) is a member of the Hepeviridae family capable of infecting humans producing a range of symptoms from mild disease to kidney failure. Epidemiological evidence suggests that hepatitis E genotype III and IV cases may be associated with the consumption of undercooked pork meat, offal and processed products such as sausages [1]. A study carried out by the Animal Health and Veterinary Laboratories Agency (AHVLA), found hepatitis E virus contamination in the UK pork production chain and that 10% of a small sample of retail pork sausages were contaminated with the virus [2]. Furthermore, studies have confirmed the presence of HEV in the food chain and the foodborne transmission of Hepatitis E virus to humans [reviewed in 5]. Likewise, Scottish shellfish at retail [6] have also been found positive for HEV viral nucleic acid and some preliminary studies indicate that the virus is also detectable in soft fruits (L Scobie; unpublished data). There are current misunderstandings in what this data represents, and these studies have raised further questions concerning the infectivity of the virus, the processing of these foods by industry and the cooking and/or preparation by caterers and consumers. There are significant gaps in the knowledge around viral infectivity, in particular the nature of the preparation of food matrices to isolate the virus, and also with respect to a consistent and suitable assay for confirming infectivity [1,3]. Currently, there is no suitable test for infectivity, and, in addition, we have no knowledge if specific food items would be detrimental to cells when assessing the presence of infectious virus in vitro. The FSA finalised a comprehensive critical review on the approaches to assess the infectivity of the HEV virus which is published [3] recommending that a cell culture based method should be developed for use with food. In order to proceed with the development of an infectivity culture method, there is a requirement to assess if food matrices are detrimental to cell culture cell survival. Other issues that may have affected the ability to develop a consistent method are the length of time the virally contaminated sample is exposed to the cells and the concentration of the virus present. In most cases, the sample is only exposed to the cells for around 1 hour and it has been shown that if the concentration is less that 1x103 copies then infection is not established [3,5,10,11].
Perceptions of English and Literature Department Students on Lecturer’s Feedback for Critical Book Review (CBR)
Authors: Saragih Bahagia , Saragih Anggraini Thesisia , Nuran Ade Aini , Saragih Ade Farida Hanim , Natsir Muhammad
Published: October 2022

This study aims to analyze Perceptions of English and Literature Department Students perceptions on lecturer’s feedback for Critical Book Review (CBR). A descriptive qualitative design was used in this study. The data sources are all students outside the English Education study program who take 5 courses, namely Curriculum and Textbook Analysis, Translation in Language Teaching, English Culture in ELT, Technology in ELT and Management of English Based Institution. The data are the results of questionnaires given to students outside the Study Program who are conducting the student exchange program (Permata). Research shows that students feel helped by the feedback provided by the lecturer in the form of corrections, criticisms, suggestions, and providing solutions either orally or in writing. The reason why lecturers provide feedback is to measure students' abilities in doing CBR assignments.
Characterization of two novel neutral sphingomyelinase 2 inhibitors in endosomal sorting and Extracellular Vesicle biogenesis
Authors: Choezom Dolma , Gross Julia Christina
Published: October 2022

Sphingomyelinase hydrolyzes the phosphodiester bond of the sphingomyelin to ceramide and phosphorylcholine and have been involved in extracellular vesicle (EV) biogenesis and more recently in membrane repair. Here we describe an initial testing of two recently discovered neutral sphingomyelinase 2 (nSMase2) inhibitors ((R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)pyrrolidin-3-yl)-carbamate (PDDC) and 2,6-dimethoxy-4-[4-phenyl-5-(2-thienyl)-1H-imidazol-2-yl]phenol (DPTIP)). PDDC and DPTIP show differential effects on cell viability, and EV marker secretion, indicating that side effects of these inhibitors on lysosomal and autophagic degradation pathways need to be considered. Moreover, similar to commonly used nSMase2 inhibitor GW4869, cell type specificity seems to play a role in the endosomal trafficking routes that can be explored to unravel mechanisms of specific EV biogenesis and secretion pathways.
An optimized protocol for the enrichment of small vesicles from murine and non-human primate heart tissue
Authors: Bleckwedel Federico , Germena Giulia , Hinkel Rabea , Zelarayán Laura C.
Published: October 2022

Over the last few years, the interest in extracellular vesicles (EVs) function has exponentially grown. However, methods for isolating these small vesicles from tissue are still not trivial. Few protocols that allow EV isolation from whole tissue samples, including the heart, are available and they are based on organ perfusion unsing Langendorff method. In this work, aiming at analysing in vivo biology of small EVs, we implemented a simple method to obtain enrichment of these vesicles from murine heart tissue. We tested a titration of Liberase for tissue digestion, which was subjected to differential ultracentrifugation combined with iodixanol cushion and presented the step-by-step procedure of this protocol. Validation was done with Nanoparticle Tracking Analysis, transmission Electron Microscope and Western Blot analysis of EV markers and organelle contaminants. Furthermore, we tested the suitability of the protocol for isolating EVs from heart tissue obtained from a pre-clinical translational non-human primate animal model. Therefore, this protocol should be suitable for isolating vesicle from human heart tissue. Additionally, this method could potentially be applied beyond heart tissue.
Innovación y Resiliencia Empresarial en el sector turístico del Rímac en el contexto de la pandemia COVID 19
Authors: Miranda Guevara Bertha , Hurtado Ramos Gualberto , Salas Pittman Quintter , Segovia Araníbar Elizabeth , Panta Sifuentes Lucia , Sandra Crispín Rossy Choccllo
Published: October 2022

El presente trabajo de investigación tuvo como objetivo analizar la innovación y la resiliencia empresarial en el sector turístico del Rímac en el contexto de la pandemia COVID 19, para alcanzar este objetivo se aplicó la metodología de enfoque cualitativo, de  método inductivo, diseño fenomenológico, cuya población estuvo conformada por 24 empresarios gastronómicos del Rímac y una muestra de 10 empresarios, como técnica se utilizó la entrevista y como instrumento una guía de preguntas semiestructurada. La investigación concluye que se puede verificar que existe una relación de asociación entre las subcategorías proceso y organizativa, debido a que las empresas se organizaban para cumplir con todos los protocolos de bioseguridad, así como en la innovación en los servicios dando como resultado un producto final, que mantiene una relación de causalidad con las subcategorías mencionadas. Además, se aprecia una relación causal provocada por la subcategoría conocimiento hacia la gestión de riesgo que produce la pandemia por Covid 19 hacía el sector turístico y se evidencia una relación de contradicción entre la subcategoría gobernanza hacía la gestión de riesgo, esto se debe a que la Municipalidad del Rímac poco o nada intervino hacía el apoyo de estas empresas incrementando el riesgo de que cierren.
Aula invertida como metodología educativa en el aprendizaje de química, Universidad Nacional de Educación. Perú-2021
Authors: Tovar Torres María Clarisa , Castro Montesino Melisa
Published: October 2022

La investigación tuvo como objetivo determinar el efecto del aula invertida como metodología educativa en el proceso de aprendizaje de la Química General e Inorgánica en los estudiantes de la facultad de Ciencias de la Universidad Nacional de Educación, habiendo participado 19 estudiantes como muestra censal, el diseño fue pre experimental en el que se evaluó el aprendizaje con instrumentos de entrada y de salida, a través de pruebas y rúbricas analíticas, y de desempeño a fin de medir las competencias conceptuales, experimentales y actitudinales, demostrándose que los niveles de logro satisfactorio y ejemplar; empezaron en lo conceptual con 5.26%, en lo procedimental 10.53%, en lo actitudinal 10.53 % y alcanzaron en lo conceptual 36.85 % en lo procedimental 94.74% en lo actitudinal 78.95%. Estos resultados evidencian que el aula invertida como metodología tuvo un efecto positivo en el aprendizaje de los estudiantes, hipótesis que a través de la prueba T de Student se aceptó con un nivel de confianza de 95%. demostrándose que el aprendizaje se fortalece con la metodología del aula invertida sobre todo en el aspecto procedimental seguido del actitudinal y conceptual, competencias de gran importancia en la ciencia química.