Predictive value of global longitudinal strain and geometry of left ventricle in patients with noncompaction cardiomyopathy

Aim. To assess the prognostic role of a decrease in longitudinal strain and an increase in the left ventricular sphericity index as predictors of NYHA class III heart failure (HF) progression, requiring hospitalization in a cohort of patients with noncompaction cardiomyopathy (NCM) in combination with dilated cardiomyopathy (DCM).Material and methods. We examined 90 patients with a combination of NCM and DCM aged 18 to 72 years (median age, 41 years; men — 73; women — 17), who, in addition to conventional echocardiographic and magnetic resonance imaging (MRI) characteristics, were studied for two-dimensional strain and global longitudinal strain (GLS) parameters and left ventricular sphericity index (SI) using cardiac MRI. The endpoints included NYHA class III HF progression, requiring hospitalization.Results. During the follow-up period (median follow-up, 36 (6; 152) months) in 59 of 90 (65,5%) patients with NCM in combination with DCM, symptoms progressed to NYHA class III HF, requiring hospitalization. Multivariate analysis showed following independent risk factors for HF-related hospitalization: a decrease in GLS <10% (hazard ratio (HR), 5,1; 95% confidence interval (CI), 1,6-16,7, p<0,007) and an increase in SI >0,5 (HR, 9,0; 95% CI, 2,2-37,8, p<0,003) .The 3-year event-free survival rate for patients with one risk factor (GLS, %<10 and SI <0,5; GLS, %>10 and SI >0,5) was 79,2±16,9% and 64,4±24,6%, respectively, while for the group with two risk factors (GLS, %<10 and SI>0,5) — 12,3%.Conclusion. Global longitudinal strain characteristics according to 2D Strain echocardiography and SI according to cardiac MRI are associated with adverse events in NCM and DCM combination and can be used to identify patients with a high risk of HF progression to NYHA class III, requiring hospitalization

Pulsations and Long-Term Light Variability of Three Candidates to Protoplanetary Nebulae

We present new photometric data and analysis of the long-duration UBV photoelectric observations for three candidates to protoplanetary objects - F-supergiants with IR-excesses located at large galactic latitudes, IRAS 18095+2704, IRAS 19386+0155, and IRAS 19500-1709. All three stars have revealed quasiperiodic low-amplitude variabilities caused by pulsations observed against the long-term trends of brightnesses. For IRAS 18095+2704=V887 Her we have found a pulsation period of 109 days and a linear trend of brightness under the constant colours if being averaged over the year timescale. The light curve of IRAS 19386+0155=V1648 Aql over 2000-2008 can be approximated by a wave with a main period of 102 days which is modulated by close frequency, with a period of 98 days, that results in brightness oscillations with a variable amplitude. V1648 Aql has also shown synchronous reddening together with a persistent rise of brightness in the V-band. IRAS 19500-1709=V5112 Sgr experiences irregular pulsations with the periods of 39 and 47 days. The long-term component of the variability of V5112 Sgr may be related to the binary character of this star.Comment: 11 pages, 6 figures, accepted for publication in Pis'ma Astron. Z

Variability of Hot Supergiant IRAS 19336-0400 in the Early Phase of its Planetary Nebula Ionization

We present photoelectric and spectral observations of a hot candidate proto-planetary nebula - early B-type supergiant with emission lines in spectrum - IRAS 19336-0400. The light and color curves display fast irregular brightness variations with maximum amplitudes Delta V=0.30 mag, Delta B=0.35 mag, Delta U=0.40 mag and color-brightness correlations. By the variability characteristics IRAS 19336-0400 appears similar to other hot proto-planetary nebulae. Based on low-resolution spectra in the range lambda 4000-7500 A we have derived absolute intensities of the emission lines H_alpha, H_beta, H_gamma, [SII], [NII], physical conditions in gaseous nebula: n_e=10^4 cm^{-3}, T_e=7000 \pm 1000 K. The emission line H_alpha, H_beta equivalent widths are found to be considerably variable and related to light changes. By UBV-photometry and spectroscopy the color excess has been estimated: E_{B-V}=0.50-0.54. Joint photometric and spectral data analysis allows us to assume that the star variability is caused by stellar wind variations.Comment: 11 pages, 6 figures, 2 tables, accepted for publication in Pis'ma Astron. Zh. (Astronomy Letters

Spectrum of mutations and their phenotypic manifestations in children and adults with long QT syndrome

Aim. To determine the spectrum of mutations in the genes responsible for the long QT syndrome (LQTS) and study their phenotypic manifestations in patients with LQTS in different age groups.Materials and methods. The study included 35 unrelated probands with a clinical diagnosis of LQTS: 23 adults (8 men) and 12 children (9 boys). There were following clinical features: syncope — 54%, positive family history for SCD — 29%, implanted cardioverter defibrillator (ICD) — 46%. All participants underwent 12-lead electrocardiography (ECG), 24-hour Holter monitoring, genealogical analysis, echocardiography and cardiac MRI. The genetic study was performed by nextgeneration sequencing (NGS) using the MiSeq system (Illumina). The quantitative comparison of two unrelated groups was carried out using the nonparametric MannWhitney U-test. The differences were considered significant at p<0,05.Results. In the examined group of 35 probands, 23 genetic variants of pathogenicity class IV and V (hereinafter referred to as) were identified. The molecular genetic variant of the disease was verified in 66% of probands. At the same time, the detection of mutations in the group with early manifestation (children) was significantly higher: 83% (10 out of 12 children) vs 57% in adults (13 out of 23). Rare genetic variants of uncertain significance (VUS, class III pathogenicity) were detected in 4 probands (11%). In the groups of children and adults with LQT1, LQT2 and LQT3, the sex distribution deviated from the 1:1 ratio. Among children, two-thirds were boys, among adults — the same proportion was represented by women. Disease manifestation time, QTc duration and adverse events risk depended on the genetic type of LQTS, intragenic localization of mutations and sex. In children, all 4 missense mutations in the KCNQ1 gene were located in transmembrane domain, and in adults, 4 mutations were in the transmembrane domain and three — in the C-terminal domain of the protein. LQT1 in boys was characterized by early manifestation, while QTc did not exceed 500 ms and there were no adverse outcomes. Two women out of 7 adults with LQT1 with mutations in the transmembrane domain had na ICD (QTc >520 ms). All patients with LQT2 (4 children, 4 adults) had QTc >500 ms. At the same time, 2 children and 3 women had an ICD. LQT3 was diagnosed only in the children subgroup (2 boys, with QTc of 510 ms and QTc of 610 ms); one of them died suddenly despite beta-blocker therapy. Four adult patients, carriers of class III pathogenicity variants, had QTc <500 ms and delayed disease manifestation (after 30 years). Three of them had episodes of clinical death with subsequent resuscitation and implantation of cardioverter defibrillator.Conclusion. The average diagnostic efficiency of mutation identification using NGS in patients with clinically manifest LQTS was 66%. At the same time, mutations were more common in the children’s group. In genotype-positive probands, the risk of adverse outcomes correlated with sex, age and the genetic variant of disease. The greatest number of adverse outcomes was observed in carriers of mutations in both KCNH2 (LQT2) and SCN5A (LQT3) genes. Variants with unknown clinical significance were identified in 4 probands (11%), which potentially allowed to confirm the diagnosis after functional tests

A Transcript Cleavage Factor of Mycobacterium tuberculosis Important for Its Survival

After initiation of transcription, a number of proteins participate during elongation and termination modifying the properties of the RNA polymerase (RNAP). Gre factors are one such group conserved across bacteria. They regulate transcription by projecting their N-terminal coiled-coil domain into the active center of RNAP through the secondary channel and stimulating hydrolysis of the newly synthesized RNA in backtracked elongation complexes. Rv1080c is a putative gre factor (MtbGre) in the genome of Mycobacterium tuberculosis. The protein enhanced the efficiency of promoter clearance by lowering abortive transcription and also rescued arrested and paused elongation complexes on the GC rich mycobacterial template. Although MtbGre is similar in domain organization and shares key residues for catalysis and RNAP interaction with the Gre factors of Escherichia coli, it could not complement an E. coli gre deficient strain. Moreover, MtbGre failed to rescue E. coli RNAP stalled elongation complexes, indicating the importance of specific protein-protein interactions for transcript cleavage. Decrease in the level of MtbGre reduced the bacterial survival by several fold indicating its essential role in mycobacteria. Another Gre homolog, Rv3788 was not functional in transcript cleavage activity indicating that a single Gre is sufficient for efficient transcription of the M. tuberculosis genome

Influence of Electrical Potential on Mechanical Properties of Commercially Pure Titanium

The influence of the electric potential on the mechanical properties of commercially pure titanium was studied. At the range from 0 to 0.1 V microhardness increases to 11 %, compared with the initial state. The elastic modulus reaches a maximum value at 1 V, exceeding »3 times the initial value.В работе исследовано влияние электрического потенциала на механические свойства технически чистого титана марки ВТ1–0. Установлено, что в интервале от 0 до 0,1 В микротвердость увеличивается до 11 % по сравнению с исходным состоянием. Модуль упругости достигает максимального значения при 1 В, превышающего в »3 раза значение в исходном состоянии.Исследование выполнено по гранте при финансовой поддержке РФФИ в рамках научного проекта № 19–32–50036

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Genetic Variability of Human Respiratory Syncytial Virus A Strains Circulating in Ontario: A Novel Genotype with a 72 Nucleotide G Gene Duplication

Human respiratory syncytial virus (HRSV) is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010–2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome