Meso-substituted cationic 3- and 4-N-Pyridylporphyrins and their Zn(II) derivatives for antibacterial photodynamic therapy

Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy (APDT) is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms. Among the photosensitizers (PSs), compounds based on cationic porphyrins/ metalloporphyrins are most successfully used to inactivate microorganisms. Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia. The aim of this work was to determine and test the most effective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms. It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria, including the methicillin-resistant S. aureus strain. Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs. The effectiveness of these Zn-metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation. It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors: The presence in the porphyrin macrocycle of a positive charge (+4), a central metal atom (Zn2+) and hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen. The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins can find wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APD

Boosting the Power Generation in Wind and Hydro Power Production

When approaching a conventional wind turbine, the air flow is slowed down and widened. This results in a loss of turbine efficiency. In order to exploit wind or water flow power as effectively as possible, it was suggested that the turbine should be placed inside a shroud, which consists of 4 wing-shaped surfaces. Two internal air foils improve the turbine performance by speeding up the flow acting on the turbine blades, two external wings create a field of low pressure behind the turbine, thus, helping to draw more mass flow to the turbine and avoid the loss of efficiency due to flow deceleration. The system accumulates kinetic energy of the flow in a small volume where the smaller (and therefore, cheaper) turbine can be installed. A smaller system can be installed inside the bigger one, which would help to accumulate even more kinetic energy on the turbine. This method implies kinetic energy summation with local flow redistribution. Both experiments and CFD simulations demonstrate a significant increase in velocity and generated mechanical power in comparison to those for a bare turbine

Pediatric bacteremia and CNS infections associated with <i>klebsiella pneumoniae</i>: molecular genetic characteristics and clinical features

Klebsiella pneumoniae is one of the most significant and life-threatening pathogen of nosocomial infections. This opportunistic microorganism can cause infections of the bloodstream, respiratory tract, urinary tract, skin and soft tissues, inflammation of meninges of the brain and spinal cord, leading to elevated hospital mortality. The purpose of our study was a retrospective analysis of molecular genetic characteristics of K. pneumoniae isolated from blood and liquor samples as well as to describe clinical features in bacteremia and CNS infections. According to the results of assessed clinical data, K. pneumoniae isolates were selected from 64 children suffered from surgical pathology (congenital heart defects — 30%, abdominal pathology — 39%, severe combined trauma — 12%) and somatic diseases accompanied by antibacterial and/or glucocorticosteroid therapy — 14%. The minimum suppressive concentrations of antibiotics were determined by the broth micro-dilution method. Carbapenemases were detected by real time polymerase chain reaction. Virulence genes and capsule serotypes K1/K2 were assessed by multiplex PCR. Biofilms were grown using flat-bottomed polystyrene plates, followed by coloring, fixation, elution and data detection. The population diversity was assessed by multilocus sequence typing. Bacteremia and CNS infections associated with K. pneumoniae were fatal in 25% of cases. A substantial portion of the isolates demonstrated the phenotype of extremely drug resistance (XDR) — 43%, the phenotype of multidrug resistance (MDR) was shown in 16% of the isolates. The blaCTX-M cephalosporinase gene was found in 85% of the strains. The main determinant of resistance to carbapenems was the blaOXA-48 gene (33%); the blaNDM gene was detected in 9% of strains. The combination of blaOXA-48 and blaNDM was found in 7% of isolates. The study of biofilm production showed that moderate ability to form biofilms was shown in 61%, strong — 21%, and weak — 15% isolates. Two isolates (3%) did not form biofilms. The virulence genes entB and mrkD were detected in 100% of isolates, ybtS — in 78%. The iutA gene was found in 18% of the strains. Two isolates showed the presence of the kfu gene. Seven isolates belonged to the K2 serotype. 27 different genotypes were found in K. pneumoniae isolates examined. The most common were: ST307 — 21%, ST395 — 12%, ST48 — 7%, ST39 — 6% and ST29 — 6%. Infections of the bloodstream and central nervous system associated with K. pneumoniae have great importance in clinical practice. This microorganism is able to long persist on biotic and abiotic surfaces, has a wide natural and acquired resistance to antibiotics

Genomic features of resistant <i>Klebsiella pneumonia</i>, isolated from the bloodstream and cerebrospinal fluid of pediatric hospital patients

Introduction. Carbapenemase-producing Klebsiella pneumoniae (CP-Kp), which are international high-risk clones, have become a problem of utmost importance. CP-Kps, adapting to the hospital environment, evolve into convergent pathotypes. Such variants combine traits of two genetic lineages: multidrug resistant (MDR) and hypervirulent. The pathotypes, along with MDR K. pneumoniae, pose an exceptional threat to young patients during systemic infection. The objective of this study is the detailed molecular genetic analysis of MDR isolates of K. pneumoniae detected during the monitoring of resistant Gram-negative bacteria at the National Medical Research Center for Children’s Health in 2014–2021. Materials and methods. Whole-genome sequencing with a subsequent bioinformatics analysis of eight MDR isolates from the bloodstream and cerebrospinal fluid. Results. MDR isolates belonged to 4 sublineages (SL): SL307, SL395, SL29 and SL1198. In the genomes of 6 pangrug-resistant (PDR) isolates, genes associated with resistance to all categories of antibiotics recommended for Enterobacteriaceae therapy were identified. Plasmids were present in all genomes. In 6 isolates, plasmids contained heavy metal ion resistance operons in addition to antibiotic resistance genes. Prophages within the plasmids were also involved in the transfer of resistance genes. The ST395 isolate from the cerebrospinal fluid belonged to the convergent pathotype in terms of resistance and virulence. Comparison of genomes within SLs revealed recombination events in the K- and O-locus regions and the Yersiniabactin operon. Conclusion. Thus, in a sample of resistant K. pneumoniae isolated from bloodstream and cerebrospinal fluid, 6 PDR isolates were detected, one of which belongs to the convergent pathotype ST395

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Первичная цилиарная дискинезия у детей

The article presents current approaches to medical care delivery in children with primary ciliary dyskinesia. The genetic heterogeneity of the disease causes the variability of pathological symptoms in clinical practice. The most common clinical manifestation in children is the frequent inflammatory diseases of the upper and lower respiratory tract which are registered in the majority of patients, especially in young children. However, the diagnosis is often untimely due to the low disease awareness among medical specialists. The article describes the algorithm for differential diagnostic search in detail, presents approaches to the treatment and management of pediatric patients with primary ciliary dyskinesia. The material is based on clinical recommendations developed and approved by the professional association «Union of Pediatricians of Russia»; recommendations were updated in 2018.Авторами представлены актуальные подходы к оказанию медицинской помощи детям с первичной цилиарной дискинезией. Генетическая неоднородность данного заболевания обусловливает вариабельность патологических симптомов в клинической практике. Наиболее распространенное проявление болезни у детей — частые воспалительные заболевания верхних и нижних дыхательных путей, которые регистрируются у большинства пациентов, особенно у детей раннего возраста. При этом диагноз болезни зачастую устанавливается несвоевременно вследствие невысокой осведомленности специалистов о данной нозологии. В статье подробно изложен алгоритм дифференциально-диагностического поиска, представлены подходы к лечению и ведению пациентов детского возраста с первичной цилиарной дискинезией. Материал основан на клинических рекомендациях, ранее разработанных и утвержденных профессиональной ассоциацией «Союз педиатров России», актуализированных и обновленных в 2018 году

The implementation of inclusive education in preschool educational institutions of Russia

The article considers the problem of inclusion through the example of preschool educational institutions. In order to determine and scientifically substantiate structural and pedagogical conditions for the inclusion of children with impaired psychophysical development in a preschool educational institution, an ascertaining experiment was conducted in four preschool institutions. It was revealed that many problems had not been previously diagnosed for a number of reasons and, accordingly, the problem was not addressed. Most educators and parents do not know children development standards and, therefore, are not able to bring the problem into sharp focus or do not take it seriously.El artículo considera el problema de la inclusión a través del ejemplo de las instituciones educativas preescolares. Con el fin de determinar y corroborar científicamente las condiciones estructurales y pedagógicas para la inclusión de niños con problemas de desarrollo psicofísico en una institución educativa preescolar, se realizó un experimento en cuatro instituciones preescolares. Se reveló que muchos problemas no habían sido diagnosticados previamente por varias razones y, en consecuencia, el problema no fue abordado. La mayoría de los educadores y los padres no conocen los estándares de desarrollo infantil y, por lo tanto, no son capaces de enfocar el problema o no lo toman en serio

Coherent fluctuation nephelometry as a promising method for diagnosis of bacteriuria

Objectives: Specialized analyzers are used to automate the diagnosis of bacteriuria in laboratory practice. They are based on analysis of microorganisms concentration in urine samples or recording the growth of urine microflora. Coherent fluctuation nephelometry (CFN) has high sensitivity and allows analyzing both parameters simultaneously. The aim of the study is to compare the effectiveness of CFN-based and flow cytometry based analyzers. Design and methods: Total 117 urine samples from children were studied in parallel using the CFN-analyzer and UF-1000i (Sysmex), the results were confirmed by conventional microbiological methods. Results: In 21 urine samples (18%), significant bacteriuria was determined (≥104 CFU/ml). The best diagnostic indicators were obtained while testing urine samples using the CFN-analyzer. The most efficient bacteriuria diagnosis is achieved by simultaneous analyses of microorganisms concentration in urine and growth of urine microflora (sensitivity – 95.2%, specificity – 96.9%, positive predictive value – 87%, negative predictive value – 98.9%, diagnostic odds ratio – 81.7, positive likelihood ratio – 30.5, negative likelihood ratio– 0.049, area under curve in ROC-analysis – 0.987). The CFN-analyzer allows the preliminary selection of negative urine samples, which do not require further analysis by conventional microbiological methods, thereby decreasing the number of cultures by 80.3%. Conclusions: This study suggests that the CFN-analyzer is the effective tool for bacteriuria screening in children. Keywords: Coherent fluctuation nephelometry, Bacteriuria, UF-1000i, Urinary tract infection, Childre

SEROTYPES AND ANTIMICROBIAL SUSCEPTIBILITY OF NASOPHARYNGEAL PNEUMOCOCCI ISOLATED FROM CHILDREN IN 2010–2016: A RETROSPECTIVE COHORT STUDY

Background. Pneumococci (Streptococcus pneumoniae) represent major pathogens that cause acute infections in children. Objective. Our aim was to analyze dynamics of the distribution of nasopharyngeal pneumococcal serotypes and their antimicrobial susceptibility in children. Methods. A retrospective cohort study was conducted. We examined nasopharyngeal pneumococci isolated from children getting care at the National Medical Research Center of Children’s Health (Moscow) in 2010–2016. Serotyping was performed using specific antisera and/or by molecular typing employing PCR. Susceptibility to oxacillin (OXA), erythromycin (ERY), clindamycin (CLI), trimethoprim/sulfamethoxazol, chloramphenicol and tetracycline was tested by the disk diffusion method. In 2013–2016, penicillin (PEN), amoxicillin (AMX), ERY and CLI minimal inhibitory concentrations (MIC) were measured. Results. A total of 1,111 pneumococcal isolates were examined; the sample was obtained from children with a median age of 4 years (P25–P75, 2.4–6.5 years). We identified 48 pneumococcal serotypes; six leading serotypes were serotypes 3, 6А, 6В, 14, 19F and 23F aggregating a proportion of 63.2% in the overall distribution. From 2010 to 2016, the distribution of serotypes has not changed. Wherein, 13-valent pneumococcal conjugate vaccine covered 74% of serotypes in children under 5 years. The five leading serotypes (6А, 6В, 14, 19F, 23F and serotype 19A) had the highest resistance rate. Within 2010–2016, the proportion of OXA- and ERY-resistant pneumococci grew from 21.3% to 35.9% and from 24.5% to 36.9%, respectively. The majority (81.3%) of ERY-resistant isolates possessed an MLSB-phenotype, i. e. were resistant to macrolides, lincosamides, and streptogramin B. In 2013–2016, the rate of PEN- and AMX-resistant pneumococci was 34.6% and 3.5%, respectively. Conclusion. Within the seven year study period, no major shifts in the nasopharyngeal pneumococcal serotype distribution were observed. The pneumococci remained highly susceptible to AMX, but activity of macrolides was significantly reduced. Considering the leading mechanism of macrolide resistance, the use of any macrolides or lincosamides for empiric treatment of pneumococcal infections in children is questionable