The state and prospects of development of national higher pharmaseutical education

The paper considers the materials of the Pharmacists Summit and International Pharmaceutical Congresses, in particular, the issue of achieving quality pharmaceutical education. It shows cause of the proper training process of pharmacy sector specialists in accordance with current state and requirements of the society and suggests a model of professional pharmaceutical education. According to the authors of the paper, the implementation of education quality in Ukraine calls for, first, professionally educated personnel in the pharmacy sector of healthcare; second, proper academic and university infrastructure for training future specialists within the system of higher pharmaceutical education; third, ensuring the high quality of higher pharmaceutical education on the basis of implementing the competence approach and taking into account international experience on pharmacy development. Increasing significance of the pharmacy branch in Ukraine is directly linked to the quality of training of pharmacy specialists, continuous improvement of the content of their education, implementation of new educational technologies, adapting higher pharmaceutical education to European standards. According to the authors, an important condition of ensuring effective professional training of future pharmacy specialists within the national system of higher pharmaceutical education is the following: firstly, considering public demand to the level of healthcare services, disease prevention; secondly, implementing the productive global experience on introducing customer service standards. The established prospects of the development of national higher pharmaceutical education include: 1) the adoption of ethical principles of training Masters of Pharmacy within the system of higher pharmaceutical education; 2) focus on European pharmacy standards which are based on high customer service standards; 3) improvement of the content of pharmacy specialist education taking into account the development of national pharmaceutical production; 4) ensuring the development of the clinical direction within the system of general pharmacist training

Clade-Specific Distribution of Antibiotic Resistance Mutations in the Population of Mycobacterium tuberculosis - Prospects for Drug Resistance Reversion

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a leading cause of death in humans worldwide. The emergence of antibiotic-resistant strains of Mtb is a threat to tuberculosis control. A general belief is that drug resistance is acquired by Mtb during antibiotic treatment by accumulation of spontaneous mutations. Also, it is known that the drug resistance mutations (DRM) have an associated fitness cost, reducing the transmissibility and virulence of resistant strains. In this work we show that many canonical DRM are clade specific; i.e. they occur only in specific genetic lineages of Mtb and depend on a specific genetic context necessary for the reduction of the fitness cost and sustainability of the drug resistance phenotype. Dependence of the drug resistance on occurrence of genetic variants of multiple genes and specific activities of the encoded proteins allows combating the drug resistance by impairing the global genetic context. A new drug, FS-1, reverses antibiotic resistance by compromising this genetic context and aggravating the fitness cost of DRM

Comparative genomics of Listeria species recovered from meat and food processing facilities

DATA AVAILABILITY : The data sets generated during and/or analyzed during the current study are available in the NCBI Sequence Read Archive (SRA) repository, BioProject ID accession number PRJNA804318 and the draft genomes are available at BioProject ID accession number PRJNA863749.Listeria species (spp.) are contaminants that can survive in food, on equipment, and on food processing premises if appropriate hygiene measures are not used. Homologous stress tolerance genes, virulence gene clusters such as the prfA cluster, and clusters of internalin genes that contribute to the pathogenic potential of the strains can be carried by both pathogenic and nonpathogenic Listeria spp. To enhance understanding of the genome evolution of virulence and virulence-associated properties, a comparative genome approach was used to analyze 41 genome sequences belonging to L. innocua and L. welshimeri isolated from food and food processing facilities. Genetic determinants responsible for disinfectant and stress tolerance were identified, including the efflux cassette bcrABC and Tn6188_qac_1 disinfectant resistance determinant, and stress survival islets. These disinfectant- resistant genes were more frequently found in L. innocua (12%) than in L. welshimeri (2%). Several isolates representing the presumed nonpathogenic L. innocua still carried virulence-associated genes, including LGI2, LGI3, LIPI-3, and LIPI-4 which were absent in all L. welshimeri isolates. The mobile genetic elements identified were plasmids (pLGUG1 and J1776) and prophages (PHAGE_Lister_vB_LmoS_188, PHAGE_Lister_LP_030_3, PHAGE_ Lister_A118, PHAGE_Lister_B054, and PHAGE_Lister_vB_LmoS_293). The results suggest that the presumed nonpathogenic isolates especially L. innocua can carry genes relevant to the strain’s virulence and stress tolerance in the food and food processing facilities. IMPORTANCE : This study provides genomic insights into the recently expanded genus in order to gain valuable information about the evolution of the virulence and stress tolerance properties of the genus Listeria and the distribution of these genetic elements pertinent to the pathogenic potential across Listeria spp. and clonal lineages in South Africa (SA).The Department of Agriculture, Land Reform and Rural Development (DALRRD).https://journals.asm.org/journal/spectrumam2023BiochemistryGeneticsMicrobiology and Plant Patholog

BEAM POSITION MONITOR SYSTEM FOR 2 MEV ELECTRON COOLER FOR COSY

Abstract The 2 MEV electron cooler for COSY storage ring FZJ is assembling in BINP. Beam position monitor (BPM) system for orbit measurements has been developed and fabricated at BINP. The system contains 2 BPMs inside the cooling section and 10 BPMs in transport channels. Continuous electron beam is modulated with a 3 MHz signal for capability to get signals from pickup electrodes. The beam current modulation can be varied in the range of 0.3-1.5 mA. The BPMs inside the cooling section can measure both electron and proton beams. It is achieved by means of switching the reference signals inside the BPM electronics. The BPM electronics provides highly precise beam position measurements. Position measurement error doesn't exceed 1 micron. Design features of the BPM system, its parameters and testing results are presented in this paper

Choice of the optimal treatment strategy for patient with multifocal bladder cancer: clinical case

Transurethral resection of bladder is the standard surgical procedure for management of bladder cancer when it is suspected. Accurate clinical staging of the disease based on the histologic findings followed by further assessment of recurrence risks and risks of disease progression are vital for defining an optimal individualized treatment strategy. Early radical cystectomy (RC) is recommended for patients suffering from superficial bladder cancer at high risk for tumor recurrence.Patients diagnosed with bladder tumors with multifocal lesions as well as with tumor size > 3 сm are related to a group of high risk for cancer progression. In this case in order to take a decision about the benefits of radical surgery, it’s essential to remember that RC is considered to be a major surgical procedure with a broad range of both intraoperative and postoperative complications. The vast majority of patients experience a lower quality of life based on the development of different types of metabolic alterations as well as the necessity for using urinals or inability to have adequate urination control. Organ-preserving therapy with active follow-up is thereby preferably to conduct on young patients with active life position.In our clinical case we confirmed that such treatment strategy allows to establish adequate control over neoplastic process with less negative impact on patients’ quality of life

Temperate bacteriophages collected by outer membrane vesicles in Komagataeibacter intermedius

The acetic acid bacteria have mainly relevance for bacterial cellulose production and fermented bio-products manufacture. The purpose of this study was to identify temperate bacteriophages in a cellulose-producing bacterial strain Komagataeibacter intermedius IMBG180. Prophages from K. intermedius IMBG180 were induced with mitomycin C and nalidixic acid. Transmission electron microscopy analysis exhibited tailed bacteriophages belonging to Myoviridae. A PCR assay targeting the capsid gene of the myoviruses proved phylogenetic position of induced phages. Nalidixic acid was poor inducer of prophages, however, it induced the OMV-like particles release. Size of OMVs depended on an antibiotic applied for phage induction and varied in the range of 30–80 and 120–200 nm. Inside some of them, tails of phages have been visible. Under conditions, inducing prophages, OMVs acted as the collectors of formed phage particles, using outer membrane receptors for phage detection (in this case, outer membrane siderophore receptor), and fulfilled therefore ―a cleaning,‖ as well as defensive functions, preventing bacteriophage spread outside population. This is the first description of myoviruses affiliated to K. intermedius, as well as outer membrane vesicles interaction with phages within this host.This research was supported by grant 47/2014 from National Academy of Sciences, Ukraine.http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-4028hb2016Biochemistr

The effect of iodine-containing nano-micelles, FS-1, on antibiotic resistance, gene expression and epigenetic modifications in the genome of multidrug resistant MRSA strain staphylococcus aureus ATCC BAA-39

Application of supplementary drugs which increase susceptibility of pathogenic bacteria to antibiotics is a promising yet unexplored approach to overcome the global problem of multidrug-resistant infections. The discovery of a new drug, an iodinecontaining nano-molecular complex FS-1, which has proven to improve susceptibility to antibiotics in various pathogens, including MRSA strain Staphylococcus aureus ATCC BAA-39TM, allowed studying this phenomenon. Chromosomal DNA and total RNA samples extracted from the FS-1 treated strain (FS) and from the negative control (NC) cultures were sequenced by PacBio SMRT and Ion Torrent technologies, respectively. PacBio DNA reads were used to assemble chromosomal DNA of the NC and FS variants of S. aureus BAA-39 and to perform profiling of epigenetically modified nucleotides. Results of transcriptional profiling, variant calling and detection of epigenetic modifications in the FS variant were compared to the NC variant. Additionally, the genetic alterations caused by the treatment of S. aureus BAA-39 with FS-1 were compared to the results of a similar experiment conducted with another model organism, E. coli ATCC BAA-196. Several commonalities in responses of these phylogenetically distant microorganisms to the treatment with FS-1 were discovered, which included metabolic transition toward anaerobiosis and oxidative/osmotic stress response. S. aureus culture appeared to be more sensitive to FS-1 due to a higher penetrability of cells by iodine bound compounds, which caused carbonyl stress associated with nucleotide damaging by FS-1, abnormal epigenetic modifications and an increased rate of mutations. It was hypothesized that the disrupted pattern of adenine methylated loci within methicillin-resistance chromosome cassettes (SCCmec) may promote excision of this antibiotic resistance determinant from chromosomes while the altered pattern of cytosine methylation was behind the adaptive gene regulation in the culture FS. The selection against the antibiotic resistance in bacterial populations caused by abnormal epigenetic modifications exemplifies possible mechanisms of antibiotic resistance reversion induced by iodine-containing compounds. These finding will facilitate development of therapeutic agents against multidrug-resistant infections.The South African National Research Foundation (NRF) and the Industrial development and industrial safety committee of the Ministry of Industry and Infrastructural Development of the Republic of Kazakhstan.http://frontiersin.org/Microbiologypm2021BiochemistryGeneticsMicrobiology and Plant Patholog

The effect of three complexes of iodine with amino acids on gene expression of model antibiotic resistant microorganisms Escherichia coli ATCC BAA-196 and Staphylococcus aureus ATCC BAA-39

DATA AVAILABILITY STATEMENT : The RNA reads generated for this study are available from the NCBI SRA database through the BioProjects PRJNA557356 and PRJNA480363 created, respectively, for the genomes of E. coli ATCC BAA-196 and S. aureus ATCC BAA-39. The links to the respective SRA Experiments are available on the BioProjectWeb-pages. The predicted X-ray structures of the complexes KS25, KS33, and KS51 were deposited at the CCDC database (https://www.ccdc.cam.ac. uk/, accessed on 26 June 2023) under accession numbers 1036607, 1036667, and 1436137, respectively.SUPPLEMENTARY INFORMATION : SUPPLEMENTARY TABLE S1. X-ray diffraction and refinement parameters; SUPPLEMENTARY TABLE S2. Genes regulated with statistical reliability (|fold change| 2.0; p-value 0.05) under the effect of iodine-containing complexes at least at one condition; SUPPLEMENTARY TABLE S3. Regulation of expression of genes involved in the central metabolism of bacteria by the three tested complexes.BACKGROUND : Iodine is a broad-spectrum antimicrobial disinfectant for topical application. Recent studies have shown promising results on the applicability of an iodine-containing complex, FS-1, against antibiotic-resistant pathogens. It was hypothesized that the antimicrobial activity of iodine-containing complexes may be modulated by the organic moiety of the complex, i.e., amino acids. METHODS : Gene regulation and metabolic alterations were studied in two model multidrug-resistant microorganisms, Staphylococcus aureus ATCC BAA-39, and Escherichia coli ATCC BAA- 196, treated with three complexes containing iodine and three different amino acids: glycine, Lalanine, and L-isoleucine. The bacterial cultures were exposed to sub-lethal concentrations of the complexes in the lagging and logarithmic growth phases. Gene regulation was studied by total RNA sequencing and differential gene expression analysis. RESULTS : The central metabolism of the treated bacteria was affected. An analysis of the regulation of genes involved in stress responses suggested the disruption of cell wall integrity, DNA damage, and oxidative stress in the treated bacteria. CONCLUSIONS : Previous studies showed that the application of iodine-containing complexes, such as FS-1, serves as a supplement to common antibiotics and can be a promising way to combat antibiotic-resistant pathogens. Current results shed light on possible mechanisms of this action by disrupting the cell wall barriers and imposing oxidative stress. It was also found that the effect of the complexes on metabolic pathways varied in the tested microorganisms depending on the organic moiety of the complexes and the growth phase when the complexes had been applied.The Ministry of Industry and Infrastructural Development of the Republic of Kazakhstan and the National Research Foundation (NRF) of South Africa.https://www.mdpi.com/journal/microorganismsam2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-03:Good heatlh and well-bein

Transcriptomics and methylomics study on the effect of iodine-containing drug FS-1 on Escherichia coli ATCC BAA-196

AIM : Promising results on application of iodine-containing nano-micelles, FS-1, against antibiotic-resistant Escherichia coli was demonstrated. MATERIALS AMD METHODS : RNA sequencing for transcriptomics and the complete genome sequencing by SMRT PacBio were followed by genome assembly and methylomics. RESULTS AND CONCLUSION : FS-1-treated E. coli showed an increased susceptibility to antibiotics ampicillin and gentamicin. Cultivation with FS-1 caused gene expression alterations toward anaerobic respiration, increased anabolism and inhibition of many nutrient uptake systems. Main targets of iodine-containing particles were cell membrane structures causing oxidative, osmotic and acidic stresses. Identification of methylated nucleotides showed an altered pattern in the FS-1-treated culture. Possible role of transcriptional and epigenetic modifications in the observed increase in susceptibility to gentamicin and ampicillin were discussed.LAY ABSTRACT : New approaches of combatting drug-resistant infections are in demand as the development of new antibiotics is in a deep crisis. This study was set out to investigate molecular mechanisms of action of new iodine-containing nano-micelle drug FS-1, which potentially may improve the antibiotic therapy of drug-resistant infections. Iodine is one of the oldest antimicrobials and until now there were no reports on development of resistance to iodine. Recent studies showed promising results on application of iodine-containing nano-micelles against antibiotic-resistant pathogens as a supplement to antibiotic therapy. The mechanisms of action, however, remain unclear. The collection strain Escherichia coli ATCC BAA-196 showing an extended spectrum of resistance to ββ-lactam and aminoglycoside antibiotics was used in this study as a model organism. Antibiotic resistance patterns, whole genomes and total RNA sequences of the FS-1-treated (FS) and negative control (NC) variants of E. coli BAA-196 were obtained and analyzed. FS culture showed an increased susceptibility to antibiotics associated with profound gene expression alterations switching the bacterial metabolism to anaerobic respiration, increased anabolism, osmotic stress response and inhibition of many nutrient uptake systems. Nucleotide methylation pattern were identified in FS and NC cultures. While the numbers of methylated sites in both genomes remained similar, some peculiar alterations were observed in their distribution along chromosomal and plasmid sequences.Sequencing was funded by the program “Study of reversion of antibiotic resistance of pathogenic microorganisms” provided by the Industrial development and industrial safety committee of the Ministry of industry and infrastructural development of the Republic of Kazakhstan. Genome assembly, annotation, bioinformatics analysis and student support were funded by the South African National Research Foundation (NRF).http://www.futuremedicine.com/loi/fmbhj2022BiochemistryGeneticsMicrobiology and Plant Patholog