Analysis of Escherichia coliSTs and resistance mechanisms in sewage from Islamabad, Pakistan indicates a difference in E. coli carriage types between South Asia and Europe

Objectives To discover the Escherichia coli STs and associated resistance mechanisms in the community in Islamabad, Pakistan by analysis of E. coli isolates in sewage. Methods One hundred and ten E. coli were isolated from sewage across the city of Islamabad without antibiotic bias and confirmed as E. coli by MALDI-TOF MS. Isolates were characterized by fumC/fimH (CH) typing and core-genome MLST. Resistance mechanisms, virulence genes, phylotypes and plasmid incompatibility types were determined in a subset of isolates by in silico analysis. The genomic position of blaCTX-M-15 was determined using S1-PFGE, probing and Nanopore MinION sequencing. Results and conclusions The most prevalent STs were ST394, ST10 and ST648, accounting for 39% of all isolates collected and were found at many sites across Islamabad. Carbapenemase genes were absent and only a single isolate of ST131 was found. The most prevalent resistance mechanisms were qnrS1 and blaCTX-M-15, with blaCTX-M-15 penetrating many STs and found in 31% of all collected isolates. However, the majority of the successful STs were blaCTX-M-15 negative indicating that resistance is not the main driver of prevalence. Twenty-three percent of blaCTX-M-15 genes were chromosomally encoded and large ISEcp1-mediated insertions included qnrS1 and several plasmid genes. In all chromosomally encoded isolates no plasmid copies of blaCTX-M-15 were found. The most prevalent ST (ST394) contained many enteroaggregative E. coli virulence genes and the fimH30 variant allele previously linked to the success of ST131

Human carriage of cefotaxime-resistant Escherichia coli in North-East India: an analysis of STs and associated resistance mechanisms

Objectives To determine the prevalence of Escherichia coli STs and associated resistance mechanisms carried by the community in North-East India. Methods E. coli (108) were isolated from sewage collected from 19 sites across the city of Silchar by plating on MacConkey agar with/without selection (50 mg/L cefotaxime). Species identification was confirmed by MALDI-TOF MS for 82 isolates. Common resistance mechanisms were determined by WGS of pooled E. coli isolates. PFGE combined with specific probes determined the presence of common resistance mechanisms in all isolates. Phylotypes, multilocus STs, core-genome multilocus STs, resistance genes and virulence genes were determined by in silico analysis of 38 genomes. Results and conclusions Analysis of isolates collected without selection (n = 33) indicated that cefotaxime resistance in E. coli was 42% (14/33) and estimated meropenem resistance at 9%. The remaining 58% (19/33) were additionally susceptible to ampicillin, trimethoprim, ciprofloxacin and aminoglycosides. The most common ST among the cefotaxime-resistant E. coli was ST167 (29%), followed by ST410 (17%) and ST648 (10%). E. coli ST131 was absent from the collection. Sixty-three isolates were resistant to cefotaxime and harboured blaCTX-M-15 [54% (34/63)] or blaCMY-42 [46% (29/63)], of which 10% (6/63) harboured both genes. Carbapenem resistance was due to blaNDM-5, found in 10/63 cefotaxime-resistant isolates, and/or blaOXA-181, found in 4/63 isolates. NDM-5 was encoded by IncX3 and/or IncFII plasmids and CMY-42 was mostly encoded by IncI plasmids. NDM-5 appears to have replaced NDM-1 in this region and CMY-42 appears to be in the process of replacing CTX-M-15

Genetic Polymorphisms Association in Restenosis of Coronary Arteries

BACKGROUND: There is a reason to believe that the polymorphism of genes encoding some enzymes and receptors plays a role in increasing of restenosis development risk. It is common knowledge that ethnicity affects the frequency of heterozygous genotypes occurrence. There is the evidence that polymorphism of the FGB gene (rs1800790) and THBD gene was determined in the ethnic group of Kazakhs with restenosis of the coronary arteries, which can be considered as genetic predictors of restenosis development. Today, the questions of the role of the genetic component in the development of coronary heart disease (CHD) remain open. AIM: Evaluation of gene polymorphism in patients with restenosis of coronary arteries after stent installation. MATERIALS AND METHODS: The group consisted of Kazakh population of the age category from 45 to 65 years of both sexes: Group I (50 persons) patients with a diagnosis of CHD, with a fixed stent and the development of restenosis during the year; Group 2 (58 persons) – with a fixed stent and no restenosis during the year. The association of genetic polymorphisms was evaluated in accordance with the case–control design based on the generalized linear model assuming a log-additive inheritance model. RESULTS: Thus, when comparing two groups using five patterns of inheritance, the following SNP were revealed: Codominant inheritance pattern – rs1045642 (p = 0.0427), dominant inheritance pattern – rs12041331 (p = 0.036088), rs13431554 (p = 0.025461), and rs1045642 (p = 0.012774), and overdominant inheritance pattern – rs12041331 (p = 0.051736), rs5918 (p = 0.057652), and rs13431554 (р = 0.036006). Thus, three SNPs associated with stenting were identified: rs7543130 (p = 0.009324), rs6785930 (p = 0.016858), and rs7819412 (p = 0.061325) and two SNPs associated with the development of restenosis after stent placement: rs1061781 (p = 0.063184) and rs342293 (p = 0.061636). CONCLUSION: The polymorphisms associated with the risk of developing restenosis after stenting were determined: Codominant inheritance pattern – one polymorphism (rs1045642, p = 0.0427); dominant inheritance pattern – three polymorphisms (rs12041331, p = 0.036088; rs13431554, p = 0.025461; rs1045642, p = 0.012774), and overdominant inheritance pattern – one polymorphism (rs13431554, p = 0.036006). Based on the hybrid machine learning approach (RuleFit), four rules were obtained for assessing the empirical risk of restenosis developing after stenting – from 20% to 40%

SPUTNIK-V REACTOGENICITY AND IMMUNOGENICITY IN THE BLOOD AND MUCOSA: A PROSPECTIVE COHORT STUDY

Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID- 19 vaccine now used in > 70 countries. Yet there is a shortage of data on this vaccine’s performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in Kazakhstan. COVID-19-free participants (n = 82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays. We observed that most of the reported adverse events were mild-to-moderate injection site or systemic reactions, no severe or potentially life-threatening conditions were reported, and dose 1 appeared to be more reactogenic than dose 2. The seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization was 83% post-dose 1, increasing to 98% post-dose 2, with the largest relative increase observed in participants without prior COVID- 19 exposure. Dose 1 boosted nasal S-IgG and S-IgA, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count. Overall, Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal. Thus, adjustments to the current vaccine dosing regimen are necessary to optimize immunization efficacy and cost-effectiveness. While Sputnik-V reactogenicity is similar to that of other COVID-19 vaccines, the induced alterations to the GRO/platelet axis warrant investigation of the vaccine’s effects on systemic immunology

PSORIASIS IS ASSOCIATED WITH ELEVATED GUT IL-1Α AND INTESTINAL MICROBIOME ALTERATIONS

Psoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut

СИМУЛЬТАННАЯ ОПЕРАЦИЯ У ПАЦИЕНТКИ С ЛЕЙОМИОМАТОЗОМ ПРАВОГО ЯИЧНИКА С ИНТРАКАРДИАЛЬНЫМ РАСПРОСТРАНЕНИЕМ: КЛИНИЧЕСКИЙ СЛУЧАЙ

HighlightsIntravascular leiomyoma with heart extension is a rare occurring condition. According to the available data, the number of cases does not exceed 30 despite many years of studies. Often cardiac hospitals cannot establish the clinical picture, so the surgeon removes only cardiac tumors, which inevitably leads to the recurrence of the tumor after a few months. AbstractLeiomyomatosis is an extremely rare disease that occurs in women of childbearing age. The development of the malignant tumor is preceded by the removal of the uterine fibroids or hysterectomy. Radical surgery guarantees the complete absence of relapses, while partial removal leads to relapses in a third of cases. We performed a reoperation on a 35-year-old patient who underwent partial removal of leiomyoma in the right atrium but 3 months later had a tumor causing severe obstruction of the right heart.Основные положенияИнтравенозная опухолевая инвазия лейомиомой, достигающей сердца, встречается редко. По данным литературы, количество случаев составляет не более 30 за долгие годы наблюдений. Зачастую диагностика в кардиостационарах не позволяет определить полную картину, поэтому хирург, как правило, удаляет лишь кардиальную часть опухоли, что неминуемо ведет к возврату опухолевой инвазии спустя несколько месяцев. АбстрактЛейомиоматоз – крайне редкое заболевание, встречаемое у женщин детородного возраста. Как правило, развитию опухоли предшествуют удаление миомы матки или гистерэктомия. Радикальная операция гарантирует полное отсутствие рецидивов, в то время как частичное удаление приводит к рецидивам в трети случаев. Нами выполнено повторное вмешательство у пациентки 35 лет, которая перенесла операцию в условиях искусственного кровообращения в объеме частичного удаления лейомиомы из правого предсердия, а спустя 3 мес. возник рецидив опухоли с признаками тяжелой обструкции правых отделов сердца

Stechkin\u27s Problem for Differential Operators and Functionals of First and Second Orders

In this paper, we present the solution to Stechkin’s problem for differential operators and functionals of first and second orders on the class of functions that are defined on a finite interval and have bounded third derivative. Two related problems are discussed: (1) finding sharp constants in the Landau–Kolmogorov inequalities, and (2) optimal recovery of an operator with the help of a set of linear operators (or arbitrary single-valued mappings) on elements of some set that are given with an error

LPS Administration Impacts Glial Immune Programs by Alternative Splicing

We performed transcriptome analysis in the hippocampus 24 h after lipopolysaccharide (LPS) administration. We observed glial-specific genes, comprised of two-thirds of all differentially expressed genes (DEGs). We found microglial DEGs that were the most numerous in LPS group. On the contrary, differential alternative splicing (DAS) analysis revealed the most numerous DAS events in astrocytes. Besides, we observed distinct major isoform switching in the Ptbp1 gene, with skipping of exon 8 in LPS group. Ptbp1 usually considered a pluripotency sustaining agent in brain embryonic development, according to the previous studies. Analyzing the splicing tune-up upon LPS exposure, we came to a supposition that the short Ptbp1 isoform de-represses immune-specific response by Ptbp1 adjusted splicing architecture. Additionally, the Ptbp3 (NOD1) immune-specific splicing factor has apparently been de-repressed by the Ptbp1 short isoform in glial cells. Notably, both the Ptbp1 and Ptbp3 genes express primarily in microglial/endothelial brain cells. We also report immune-related genes, altering their major isoforms upon LPS exposure. The results revealed immune modulating role of alternative splicing in brain