Putative histidine kinase inhibitors with antibacterial effect against multi-drug resistant clinical isolates identified by in vitro and in silico screens

Novel antibacterials are urgently needed to address the growing problem of bacterial resistance to conventional antibiotics. Two-component systems (TCS) are widely used by bacteria to regulate gene expression in response to various environmental stimuli and physiological stress and have been previously proposed as promising antibacterial targets. TCS consist of a sensor histidine kinase (HK) and an effector response regulator. The HK component contains a highly conserved ATP-binding site that is considered to be a promising target for broad-spectrum antibacterial drugs. Here, we describe the identification of putative HK autophosphorylation inhibitors following two independent experimental approaches: in vitro fragment-based screen via differential scanning fluorimetry and in silico structure-based screening, each followed up by the exploration of analogue compounds as identified by ligand-based similarity searches. Nine of the tested compounds showed antibacterial effect against multi-drug resistant clinical isolates of bacterial pathogens and include three novel scaffolds, which have not been explored so far in other antibacterial compounds. Overall, putative HK autophosphorylation inhibitors were found that together provide a promising starting point for further optimization as antibacterials

MUSICAL INTERESTS AND ACTIVITIES IN CHILDREN’S LEISURE TIME IN HUNGARY AND BULGARIA

Beneficial use of leisure time is extremely important as it helps to expand the horizons for intellectual growth, emotional experiences, and personal enrichment. The aim of this study is to establish the interests and needs for music in children’s leisure time. Music is very close to the emotional nature of children and therefore could stimulate and develop their mental and physical abilities. This report focuses on the place of music and art in students’ life and discusses how much of their free time is taken up with these pursuits. It also analyses the needs of such activities. Here the results from a study in which children between 9 to 17 years of age from Bulgaria and Hungary took part are presented. The type of musical activities preferred by the children in their leisure time and the correlation between the activities of choice and cultural differences are also studied. Understanding what music activities children favour in their leisure time is important because learning combined with the arts builds long lasting social skills and educates on tolerance, creativity and discipline. This combination when used in work with children, helps children to develop ability for better self-expression, building up confidence, concentration, integration in the group, developing imagination, recognizing the good and beautiful, and increases their chances for success in life

Risk management method for small photovoltaic plants

Risk management is necessary for achieving the goals of the organization. There are many methods, approaches, and instruments in the literature concerning risk management. However, these are often highly specialized and transferring them to a different field can prove difficult. Therefore, managers often face situations where they have no tools to use for risk management. This is the case with small photovoltaic plants (according to a definition by the Bulgarian State Energy and Water Regulatory Commission small applies to systems with a total installed power of 200 kWp). There are some good practices in the energy field for minimizing risks, but they offer only partial risk prevention and are not sufficient. Therefore a new risk management method needs to be introduced. Small photovoltaic plants offer plenty of advantages in comparison to the other renewable energy sources which makes risk management in their case more important. There is no classification of risks for the exploitation of small photovoltaic systems in the available literature as well as to what degree the damages from those risks could spread. This makes risk analysis and evaluation necessary for obtaining information which could aid taking decisions for improving risk management. The owner of the invested capital takes a decision regarding the degree of acceptable risk for his organization and it must be protected depending on the goals set. Investors in small photovoltaic systems need to decide to what degree the existing risks can influence the goals previously set, the payback of the investment, and what is the acceptable level of damages for the investor. The purpose of this work is to present a risk management method, which currently does not exist in the Bulgaria, so that the risks and the damages that could occur during the exploitation of small photovoltaic plants could be identified and the investment in such technology – justified

Specific Immunoglobulin E and G to Common Food Antigens and Increased Serum Zonulin in IBS Patients: A Single-Center Bulgarian Study

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder whose pathogenesis is considered multifactorial, including abnormal gut motility, visceral hyperreactivity, psychological factors, disturbances in the brain-gut axis, leaky gut, oxidative stress, etc. We aimed to investigate serum levels of specific immunoglobulin E and G to common food antigens and zonulin and to assess their use in clinical practice for patients with IBS. Material and methods. We included 23 participants, 15 with IBS (diagnosed according to the Rome IV criteria) and 8 healthy controls. We investigated serum levels of specific IgG antibodies to 24 food antigens, specific IgE antibodies to 20 food antigens, anti-celiac antibodies, fecal calprotectin and serum zonulin by ELISA. Results. Food-specific positive IgG antibodies were significantly higher in patients with IBS than in controls (p = 0.007). IgE-mediated allergic reactions were found in five patients with IBS; no one had anti-TG antibodies. One-third of IBS patients demonstrated a low degree of chronic inflammation (positive fecal calprotectin test > 50 ng/mL) without specific bacterial infection. Serum levels of zonulin in IBS patients were higher than in healthy controls (0.378 ± 0.13 vs. 0.250 ± 0.14 ng/mL, p = 0.0315). However, no correlations between clinical symptoms and zonulin levels were found. Conclusion. The mechanisms of IgG hypersensitivity and low degree inflammation in IBS and elevated zonulin may contribute to multifactor pathogenesis in IBS

Specific Immunoglobulin E and G to Common Food Antigens and Increased Serum Zonulin in IBS Patients: A Single-Center Bulgarian Study

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder whose pathogenesis is considered multifactorial, including abnormal gut motility, visceral hyperreactivity, psychological factors, disturbances in the brain-gut axis, leaky gut, oxidative stress, etc. We aimed to investigate serum levels of specific immunoglobulin E and G to common food antigens and zonulin and to assess their use in clinical practice for patients with IBS. Material and methods. We included 23 participants, 15 with IBS (diagnosed according to the Rome IV criteria) and 8 healthy controls. We investigated serum levels of specific IgG antibodies to 24 food antigens, specific IgE antibodies to 20 food antigens, anti-celiac antibodies, fecal calprotectin and serum zonulin by ELISA. Results. Food-specific positive IgG antibodies were significantly higher in patients with IBS than in controls (p = 0.007). IgE-mediated allergic reactions were found in five patients with IBS; no one had anti-TG antibodies. One-third of IBS patients demonstrated a low degree of chronic inflammation (positive fecal calprotectin test > 50 ng/mL) without specific bacterial infection. Serum levels of zonulin in IBS patients were higher than in healthy controls (0.378 ± 0.13 vs. 0.250 ± 0.14 ng/mL, p = 0.0315). However, no correlations between clinical symptoms and zonulin levels were found. Conclusion. The mechanisms of IgG hypersensitivity and low degree inflammation in IBS and elevated zonulin may contribute to multifactor pathogenesis in IBS

Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure

The interplay between drugs and microbiota is critical for successful treatment. An accumulating amount of evidence has identified the significant impact of intestinal microbiota composition on cancer treatment response, particularly immunotherapy. The possible molecular pathways of the interaction between immune checkpoint inhibitors (ICIs) and the microbiome can be used to reverse immunotherapy tolerance in cancer by using various kinds of interventions on the intestinal bacteria. This paper aimed to review the data available on how the antibiotic-related changes in human microbiota during colorectal cancer (CRC) treatment can affect and determine ICI treatment outcomes. We also covered the data that support the potential intimate mechanisms of both local and systemic immune responses induced by changes in the intestinal microbiota. However, further better-powered studies are needed to thoroughly assess the clinical significance of antibiotic-induced alteration of the gut microbiota and its impact on CRC treatment by direct observations of patients receiving antibiotic treatment

Endothelial Dysfunction and Pregnant COVID-19 Patients with Thrombophilia: A Narrative Review

Pregnancy with SARS-CoV-2 infection can raise the risk of many complications, including severe COVID-19 and maternal–fetal adverse outcomes. Additionally, endothelial damage occurs as a result of direct SARS-CoV-2 infection, as well as immune system, cardiovascular, and thrombo-inflammatory reactions. In this narrative review, we focus on endothelial dysfunction (ED) in pregnancy, associated with obstetric complications, such as preeclampsia, fetal growth retardation, gestational diabetes, etc., and SARS-CoV-2 infection in pregnant women that can cause ED itself and overlap with other pregnancy complications. We also discuss some shared mechanisms of SARS-CoV-2 pathophysiology and ED