CRISPR-Сas systems are widespread in bacteria and archaea. They provide adaptive immunity against bacterial phages and plasmids and exert a few important functions like regulation of gene expression, DNA repair or virulence formation. We have analyzed the CRISPR-Cas systems of 7 Mусоbacterium tuberculosis lineages with fully sequenced genomes, namely Beijing, B0/W-148, EAI, Haarlem, Ural, LAM, and S. The CRISPR-Cas systems present in the analyzed genomes belong to type III-A. M. tuberculosis lineages differ in their CRISPR-Cas structure; in the Beijing lineage a part of the system is reduced. We have conducted a search for the functionally related partners and compensatory mechanisms of cas-genes using a method of phylogenetic profiling. The obtained phylogenetic profiles show that some genes have undergone similar evolutionary events. The reduction of the system’s part in the Beijing lineage was accompanied by at least two evolutionary losses and one acquisition of genome regions. Exploration of alternative CRISPR-Cas functions in M. tuberculosis and their possible associations with other gene systems remains an exciting challenge.
VIEWS 5205
A molecular marker for the risk of endometriosis recurrence can help to customize a post-operative treatment plan for an individual patient. The aim of this study was to compare the expression of genes coding for estradiol (mER, ERα, ERβ) and progesterone (PGRmC1, mPR, РR-А, PR-B) receptors in first-time and relapsing patients with ovarian endometriosis. Our study included 94 women of reproductive age with ovarian endometriosis: 82 first-time and 12 relapsing patients. The expression of genes coding for steroid receptors was measured using reverse transcription polymerase chain reaction. Recurrent conditions were characterized by a change in the expression of estrogen receptors and unchanged expression of progesterone receptors. Expression of mER in the tissue of patients with first-time endometriosis was 15.09 ± 1.18. Patients undergoing recurrence demonstrated a 3-fold increase in mER expression (from 15.09 ± 1.18 to 44.45 ± 9.1). Also, in such patients ERβ expression was 5 times higher increasing from 11.71 ± 0.22, which is an average value for first-time patients, to 10.02 ± 3.81, while ERα expression surged 7-fold from 10.47 ± 1.05 to 1.68 ± 0.55 (p < 0.05). Transcription of the studied receptors in the pathological tissue depended on the stage of the disease: in relapsing patients expression of estradiol receptors underwent some changes, while expression profile of progesterone receptors remained unchanged. Sensitivity of endometrial tissue to gestogens is clinically important and serves as a basis for a successful hormone-based relapse prevention.
VIEWS 4870
Perioperative antimicrobial prophylaxis (PAP) involves administration of antimicrobial agents (AMA) to patients undergoing a surgical intervention and aims to reduce the risk of postoperative infectious complications, especially at surgical sites. In the present work we assess efficiency and safety of AMA used for prevention of postoperative infectious complications. In the course of our study we pre-analyzed 576 medical histories of post-op patients aged 18 to 87 years (mean age М ± SD was 57.4 ± 14.5 years), of which 347 (60.2%) were male and 229 (39.8%) female. Only 481 histories were selected for final analysis. We assessed the choice of antibacterial therapy, the frequency of adverse reactions (AR) and infectious complications and the type of the latter. PAP regimens were consistent with the official guidelines in 207 (43.04%) cases. PAP recommendations were ignored in 274 cases (56.96%), and the timing was wrong in 364 cases (75.7%). Incorrect dosages were administered in 225 cases (46.8%). We also discovered an association between irrational PAP regimens and 1) the length of patient’s stay in the intensive care unit (р = 0.003 and р < 0.005), 2) the frequency of reoperations associated with infection (р = 0.001), 3) mortality rates (р = 0.002), and 4) isolation of strains with multidrug resistance (р = 0.016). We conclude that PAP regimens for the inpatients of surgical wards are often compromised by failure to comply with the official guidelines, wrong timing and incorrect dosage, which negatively affects hospital statistics.
VIEWS 5040
Ichthyosis vulgaris (IV), a serious skin condition that runs in families, is actively studied worldwide. In this work we aimed to evaluate the prevalence of IV and frequency of two FLG mutations R501X and 2282del4 in the population of the Rostov region. Our genetic epidemiology study of hereditary monogenic disorders covered a total of 497,460 residents of 12 districts to identify 230 separate nosological entities. In the course of the analysis, we calculated the prevalence of IV per district and in the entire region and compared our findings with the results of earlier studies. The average prevalence of IV in the Rostov region was 1:5,025, which is consistent with the average prevalence of the disease across Russia (1:5,151). Tselinsky and Millerovsky districts demonstrated the highest prevalence rates (1:1,942 and 1:2,032, respectively). To evaluate the frequency of two FLG mutations R501X and 2282del4, we assayed the samples of 58 patients with IV and 127 healthy unelated controls by PCR followed by the restriction fragment length polymorphism analysis. In patients with IV, the frequency of the 2282del4 mutation was 48.28%, which is in line with European figures and also 30 times higher than in the controls (1.58%), suggesting the pathogenicity of the mutation. The R501X mutation was not identified both in patients with IV and healthy controls.
VIEWS 4797