Exploring Prognostically Significant Factors in COVID-19-Associated Pulmonary Fibrosis after Adaptive Lung Ventilation.

Background: Research data on hospitalized coronavirus 2019 (COVID-19) survivors indicate the persistence of symptoms, radiological abnormalities, and physiological disorders months after the initial infection. Given the scale of the ongoing pandemic, a substantial number of patients with severe residual pulmonary fibrosis (PF) and oxygen dependence are anticipated. Currently, the search for risk factors associated with the development of fibrotic radiological abnormalities after moderate to severe COVID-19 is underway. Furthermore, the extent to which computed tomography (CT) data correlate with postdischarge symptoms and physical functions remains unclear. This study aimed to characterize patients experiencing persistent pulmonary consequences after hospital discharge. We examined clinical, radiological, and laboratory predictors of pulmonary fibrosis after COVID-19 infection. Methods: We retrospectively evaluated fibrosis-like lung changes and their prognostic factors in COVID-19 survivors. Our study included 77 patients with laboratory-confirmed COVID-19 who received inpatient treatment at City Clinical Hospital No. 1 in Almaty between November and December 2020. We assessed patients during the acute phase of the disease and again 6 to 8 months after discharge using high-resolution computed tomography (CT). Patients were classified into 2 cohorts based on semi-quantitative analysis of subsequently added tomograms-those with radiological fibrosis-like abnormalities (main group) and those who had recovered (control group). Results: Parenchymal cords, irregular interfaces, reticulation, and traction bronchiectasis were common CT findings among all COVID-19 patients. Our study focused on patients who developed pulmonary fibrosis within 1 month after the onset of the disease. After 6 to 8 months, fibrosis-like lung changes persisted in 49.35% of patients (leading group), while 50.65% showed disease resolution (control group). Age, body mass index, high interleukin-6 (IL-6) levels, low IO levels, and the need for mechanical ventilation were identified as prognostic indicators for the persistence of pulmonary fibrosis. Conclusion: Our study revealed that pulmonary function can return to normal in over half of COVID-19 patients 8 months after infection onset. Despite advancements in COVID-19 treatment, there remains a significant knowledge gap in managing long-term effects, especially pulmonary fibrosis. Continued clinical trials and research on post COVID-19 fibrosis are essential to prevent early mortality due to the long-term impacts on these patients.

Hb Ryazan: An Elongated C-Terminal ß-Chain Due to a New Frameshift Mutation, HBB: c.396delG p.Val133Trpfs*25.

We identified a novel abnormal hemoglobin variant caused by a frameshift mutation at nucleotide position 396 in exon 3 of the ß-globin gene (HBB): NM_000518:c.396delG. This variant causes an emergence of alternative amino acid sequence starting at codon 133 and a new stop codon formed in the 3' untranslated region (3'UTR) of the HBB gene at amino acid position 158. This ß-globin gene variant was identified in a woman with a long history of hemolytic anemia. We named this variant Hb Ryazan after the proband's city of origin.

SARS-CoV-2 Variants Monitoring Using Real-Time PCR.

According to the temporary recommendations of the 2021 World Health Organization (WHO), in addition to whole-genome sequencing, laboratories in various countries can also screen for known mutations utilizing targeted RT-PCR-based mutation detection assays. The aim of this work was to generate a laboratory technique to differentiate the main circulating SARS-CoV-2 variants in 2021-2022, when a sharp increase in morbidity was observed with the appearance of the Omicron variant. Real-time PCR methodology is available for use in the majority of scientific and diagnostic institutions in Russia, which makes it possible to increase the coverage of monitoring of variants in the territories of all 85 regions in order to accumulate information for the Central Services and make epidemiological decisions. With the methodology developed by the Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (FSSCRP Human Wellbeing) (CRIE), more than 6000 biological samples have been typed, and 7% of samples with the Delta variant and 92% of samples with the Omicron variant have been identified as of 25 August 2022. Reagents for 140,000 definitions have been supplied to regional organizations.

Summary and Trends of the Russian Gonococcal Antimicrobial Surveillance Programme, 2005 to 2016.

The Russian Gonococcal Antimicrobial Surveillance Programme (RU-GASP) was established in 2004 and operated continuously during the years from 2005 to 2016. The aims of this study were to summarize the RU-GASP results over this 12-year period and evaluate the trends in Neisseria gonorrhoeae antimicrobial resistance in Russia. In total, 5,038 verified N. gonorrhoeae isolates from 40 participating regions were tested for susceptibility to six antimicrobials via an agar dilution method. DNA loci involved in antimicrobial resistance were identified via minisequencing or DNA microarray techniques. From 2005 to 2016, increasing susceptibility to penicillin G (from 22.6% to 63.0%), tetracycline (from 34.8% to 53.0%), and ciprofloxacin (from 50.6% to 68.6%) was observed, but resistance to these drugs remained high. The proportions of isolates nonsusceptible to azithromycin and spectinomycin peaked in 2011 and decreased thereafter. Of the isolates, only 6 and 23 were identified as nonsusceptible to ceftriaxone according to the CLSI definitions and EUCAST breakpoint (0.57% of the total population), respectively. Comparison of N. gonorrhoeae antimicrobial resistance genetic determinants in 2005 versus those in 2016 showed a significant decrease in the number of isolates carrying chromosomal mutations. The proportion of isolates with wild-type genotypes increased from 11.7% in 2005 to 30.3% in 2016. Thus, the RU-GASP can be considered a successful gonorrhea surveillance program, and the current state of N. gonorrhoeae antimicrobial resistance in Russia is less serious than that in other WHO GASP regions.

Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group.

The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5'-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5'-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing.

Silencing activity of 2'-O-methyl modified anti-MDR1 siRNAs with mismatches in the central part of the duplexes.

The thermodynamic properties of siRNA duplexes are important for their silencing activity. siRNAs with high thermodynamic stability of both the central part of the duplex and in the whole, usually display low silencing activity. Destabilization of the central part of the siRNA duplex could increase its silencing activity. However, mismatches located in the central part of the duplex could substantially decrease the amount of RNAi efficacy, hindering active RISC formation and function. In this study, we examined the impact of duplex destabilization by nucleotide substitutions in the central part (7-10 nt counting from the 5'-end of the antisense strand) of the nuclease-resistant siRNA on its silencing activity.