Genetic Basis of Early Onset Atrial Fibrillation in Patients without Risk Factors

Funding Information: This research was funded by the Latvian Council of Science, project, “The role of clonal hemato-poiesis of indeterminate potential as a potential driver of cardiovascular diseases and its associ-ation with clinical outcome”, project No. lzp-2021/1-0293. Publisher Copyright: © 2023 by the authors.Background: Atrial fibrillation (AF) is the most common arrhythmia and typically occurs in elderly patients with other cardiovascular and extracardiac diseases. However, up to 15% of AF develops without any related risk factors. Recently, the role of genetic factors has been highlighted in this particular form of AF. Aims: The aims of this study were to determine the prevalence of pathogenic variants in early-onset AF in patients without known disease-related risk factors and to identify any structural cardiac abnormalities in these patients. Materials and Methods: We conducted exome sequencing and interpretation in 54 risk factor-free early-onset AF patients and further validated our findings in a similar AF patient cohort from the UK Biobank. Results: Pathogenic/likely pathogenic variants were found in 13/54 (24%) patients. The variants were identified in cardiomyopathy-related and not arrhythmia-related genes. The majority of the identified variants were TTN gene truncating variants (TTNtvs) (9/13 (69%) patients). We also observed two TTNtvs founder variants in the analysed population—c.13696C>T p.(Gln4566Ter) and c.82240C>T p.(Arg27414Ter). Pathogenic/likely pathogenic variants were found in 9/107 (8%) individuals from an independent similar AF patient cohort from the UK Biobank. In correspondence with our Latvian patients, only variants in cardiomyopathy-associated genes were identified. In five (38%) of the thirteen Latvian patients with pathogenic/likely pathogenic variants, dilation of one or both ventricles was identified on a follow-up cardiac magnetic resonance scan. Conclusions: We observed a high prevalence of pathogenic/likely pathogenic variants in cardiomyopathy-associated genes in patients with risk factor-free early-onset AF. Moreover, our follow-up imaging data indicate that these types of patients are at risk of developing ventricular dilation. Furthermore, we identified two TTNtvs founder variants in our Latvian study population.publishersversionPeer reviewe

Subjective Sleepiness Dynamics Dataset (SSDD) Presentation: the Study of Two Scales Consistency

While the first references to the system of sleepiness assessment are associated with medical re-search and the study of the effects of drugs on sleep, currently subjective sleepiness assessment is widely used across fundamental and practically oriented studies. The Stanford Sleepiness Scale (SSS) and the Karolinska Sleepiness Scale (KSS) are often used as ground truth in sleepiness re-search. Only a few studies applied both scales and practically none aimed at studying their con-sistency and specific features. The present study is devoted to analyzing the dynamics and con-sistency of subjective sleepiness as measured by the KSS and the SSS in the adult population. A particular task of the paper is to present the Subjective Sleepiness Dynamics Dataset (SSDD) with the evening and morning dynamics of situational subjective sleepiness. A total of 208 adults took part in the experiment. The results of the study revealed that sleepiness generally increased from evening till night and was maximal at early morning. The SSS score appeared to be more sensitive to some factors (e.g., the presence of sleep problems). The SSS and KSS scores were strongly consistent with each other. The KSS showed a generally more even distribution than the SSS. SSDD continues to be collected, we are going to equalize the sample by sex, we are actively adding older people. We plan to collect a sample of 1,000 people. Currently SSDD contains a lot of in-formation that can be used for scientific research.Comment: 18 pages, 6 figures, 3 table

Metabolic Remodeling during Long-Lasting Cultivation of the Endomyces magnusii Yeast on Oxidative and Fermentative Substrates

In this study, we evaluated the metabolic profile of the aerobic microorganism of Endomyces magnusii with a complete respiration chain and well-developed mitochondria system during long-lasting cultivation. The yeast was grown in batches using glycerol and glucose as the sole carbon source for a week. The profile included the cellular biological and chemical parameters, which determined the redox status of the yeast cells. We studied the activities of the antioxidant systems (catalases and superoxide dismutases), glutathione system enzymes (glutathione peroxidase and reductase), aconitase, as well as the main enzymes maintaining NADPH levels in the cells (glucose-6-phosphate dehydrogenase and NADP+-isocitrate dehydrogenase) during aging of Endomyces magnusii on two kinds of substrates. We also investigated the dynamics of change in oxidized and reduced glutathione, conjugated dienes, and reactive oxidative species in the cells at different growth stages, including the deep stationary stages. Our results revealed a similar trend in the changes in the activity of all the enzymes tested, which increased 2–4-fold upon aging. The yeast cytosol had a very high reduced glutathione content, 22 times than that of Saccharomyces cerevisiae, and remained unchanged during growth, whereas there was a 7.5-fold increase in the reduced glutathione-to-oxidized glutathione ratio. The much higher level of reactive oxidative species was observed in the cells in the late and deep stationary phases, especially in the cells using glycerol. Cell aging of the culture grown on glycerol, which promotes active oxidative phosphorylation in the mitochondria, facilitated the functioning of powerful antioxidant systems (catalases, superoxide dismutases, and glutathione system enzymes) induced by reactive oxidative species. Moreover, it stimulated NADPH synthesis, regulating the cytosolic reduced glutathione level, which in turn determines the redox potential of the yeast cell during the early aging process

Metabolic Remodeling during Long-Lasting Cultivation of the Endomyces magnusii Yeast on Oxidative and Fermentative Substrates

In this study, we evaluated the metabolic profile of the aerobic microorganism of Endomyces magnusii with a complete respiration chain and well-developed mitochondria system during long-lasting cultivation. The yeast was grown in batches using glycerol and glucose as the sole carbon source for a week. The profile included the cellular biological and chemical parameters, which determined the redox status of the yeast cells. We studied the activities of the antioxidant systems (catalases and superoxide dismutases), glutathione system enzymes (glutathione peroxidase and reductase), aconitase, as well as the main enzymes maintaining NADPH levels in the cells (glucose-6-phosphate dehydrogenase and NADP+-isocitrate dehydrogenase) during aging of Endomyces magnusii on two kinds of substrates. We also investigated the dynamics of change in oxidized and reduced glutathione, conjugated dienes, and reactive oxidative species in the cells at different growth stages, including the deep stationary stages. Our results revealed a similar trend in the changes in the activity of all the enzymes tested, which increased 2–4-fold upon aging. The yeast cytosol had a very high reduced glutathione content, 22 times than that of Saccharomyces cerevisiae, and remained unchanged during growth, whereas there was a 7.5-fold increase in the reduced glutathione-to-oxidized glutathione ratio. The much higher level of reactive oxidative species was observed in the cells in the late and deep stationary phases, especially in the cells using glycerol. Cell aging of the culture grown on glycerol, which promotes active oxidative phosphorylation in the mitochondria, facilitated the functioning of powerful antioxidant systems (catalases, superoxide dismutases, and glutathione system enzymes) induced by reactive oxidative species. Moreover, it stimulated NADPH synthesis, regulating the cytosolic reduced glutathione level, which in turn determines the redox potential of the yeast cell during the early aging process

Spacial and temporal dynamics of the volume fraction of the colloidal particles inside a drying sessile drop

Using lubrication theory, drying processes of sessile colloidal droplets on a solid substrate are studied. A simple model is proposed to describe temporal dynamics both the shape of the drop and the volume fraction of the colloidal particles inside the drop. The concentration dependence of the viscosity is taken into account. It is shown that the final shapes of the drops depend on both the initial volume fraction of the colloidal particles and the capillary number. The results of our simulations are in a reasonable agreement with the published experimental data. The computations for the drops of aqueous solution of human serum albumin (HSA) are presented.Comment: Submitted to EPJE, 7 pages, 8 figure

Tackling a novel lethal virus: a focus on H7N9 vaccine development

Introduction: Avian-origin H7N9 influenza viruses first detected in humans in China in 2013 continue to cause severe human infections with a mortality rate close to 40%. These viruses are acknowledged as the subtype most likely to cause the next influenza pandemic. Areas covered: Here we review published data on the development of H7N9 influenza vaccine candidates and their evaluation in preclinical and clinical trials identified on PubMed database with the term ‘H7N9 influenza vaccine’. In addition, a search with the same term was done on ClinicalTrials.gov to find ongoing clinical trials with H7N9 vaccines. Expert commentary: Influenza vaccines are the most powerful tool for protecting the human population from influenza infections, both seasonal and pandemic. During the past four years, a large number of promising H7N9 influenza vaccine candidates have been generated using traditional and advanced gene engineering techniques. In addition, with the support of WHO’s GAP program, influenza vaccine production capacities have been established in a number of vulnerable low- and middle-income countries with a high population density, allowing the countries to be independent of vaccine supply from high-income countries. Overall, it is believed that the world is now well prepared for a possible H7N9 influenza pandemic

Current trends in the treatment of bronchial asthma

Bronchial asthma is a widespread disease of the respiratory system, has a significant impact on the quality of life of patients. The main objectives of the treatment of asthma is to achieve symptom control, prevent exacerbations and prevent the development of complications. The article describes approaches to the management of patients with severe asthma, the use of monoclonal antibodies in the treatment of asthma

Basics of CD8 T-cell immune responses after influenza infection and vaccination with inactivated or live attenuated influenza vaccine

Introduction: One of the essential mechanisms of virus infection control is cell-mediated cytotoxicity, which can act in an antibody-dependent or -independent fashion and is provided by different effector cells. The role of CD8 T-cells in infection control and in affecting the pathological outcome of different types of infection has been demonstrated in numerous animal studies. Despite this, their role in controlling human influenza infection is not fully understood. Especially, knowledge about their induction and turnover in human influenza infection is limited. Differences in the development of CD8 T-cells after influenza infection or immunizations should be explored in detail, in relation to the bioaccessibility of influenza antigens, site of application and distribution routes. Areas covered: This review focuses on the basics of CD8 T-cell immune response both in human influenza infection and after administration of inactivated or live attenuated influenza vaccine. Some aspects of the accessibility, distribution and presentation of influenza antigens to CD8 T-cells are described. Expert commentary: The CD8 T-cell response is an essential connection between innate and antibody-mediated responses, which are all-important for influenza control. We hypothesize that immunization with live influenza vaccine is the most straightforward artificial way to induce an efficient influenza-specific CD8 T-cell response