Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci. Here, we present a novel algorithm for extrasensitive and specific variable (V) and joining (J) gene allele inference, allowing the reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput novel allele discovery from a wide variety of existing data sets. The developed algorithm is a part of the MiXCR software. We demonstrate the accuracy of this approach using AIRR-seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) AIRR-seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRA and TRB) AIRR-seq data set, representing 134 individuals. This allowed us to assess the genetic diversity within the IGH, TRA, and TRB loci in different populations and to establish a database of alleles of V and J genes inferred from AIRR-seq data and their population frequencies with free public access through VDJ.online database.
- MeSH
- alely * MeSH
- algoritmy * MeSH
- genetická variace MeSH
- lidé MeSH
- receptory antigenů B-buněk genetika imunologie MeSH
- receptory antigenů T-buněk genetika imunologie MeSH
- sekvenční analýza DNA metody MeSH
- software * MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Health is one of the Sustainable Development Goals. The importance of health promotion is growing in the context of an aging population and increasing life expectancy. Prevention is often underestimated and neglected by citizens. This article aims to identify the socioeconomic predictors of preventive health check-ups by general practitioners in the Czech Republic, focusing on selected age groups. An original dataset is prepared based on data for 2010-2019 provided by the largest health insurance company in the Czech Republic, the General Health Insurance Company. Correlation and regression analysis methods are used to achieve the objectives. Two models are built and tested: (1) preventive examinations model and (2) preventive examinations in age group 65+ model. Based on the results, preventive medical examinations in the pensioner group depended on economic indicators, such as the average wage, employment, and gross domestic product, in the analyzed period. For the total population, overall population size, the average age, urbanized area, and level of education play a key role. The results reveal a difference between the general population group and the 65+ population group. Government interventions and health policies promoting prevention should consider using appropriate incentive policy instruments targeting the 65+ population to prolong active life in senior age.
- Publikační typ
- časopisecké články MeSH
The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.
- MeSH
- adjuvancia imunologická MeSH
- aplikace intranazální MeSH
- chitosan * chemie MeSH
- glykoproteiny MeSH
- imunizace MeSH
- imunoglobulin A MeSH
- Muromegalovirus * MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nanočástice * chemie MeSH
- slizniční imunita MeSH
- vakcíny * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: We aimed to evaluate the prognostic impact of renal insufficiency and fluctuation of glomerular filtration observed during hospitalization for heart failure (HF). METHODS: We followed 3,639 patients hospitalized for acute HF and assessed the mortality risk associated with moderate or severe renal insufficiency, either permanent or transient. RESULTS: After adjustment, severe renal failure defined as estimated glomerular filtration (eGFR) <30 mL/min indicates ≈60% increase in 5-year mortality risk. Similar risk also had patients with only transient decline of eGFR to this range. In contrast, we did not observe any apparent mortality risk attributable to mild/moderate renal insufficiency (eGFR 30-59.9 mL/min), regardless of whether it was transient or permanent. CONCLUSION: Even transient severe renal failure during hospitalization indicates poor long-term prognosis of patients with manifested HF. In contrast, only moderate renal insufficiency observed during hospitalization has no additive long-term mortality impact.
- MeSH
- hodnoty glomerulární filtrace MeSH
- hospitalizace MeSH
- ledviny MeSH
- lidé MeSH
- prognóza MeSH
- renální insuficience * komplikace MeSH
- srdeční selhání * komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Migréna je časté neurologické onemocnění, které postihuje značnou část celosvětové populace. Nedávným pokrokem v léčbě tohoto onemocnění v České republice se stalo schválení úhrady pro rimegepant v akutní léčbě migrény. Rimegepant, lék ze skupiny gepantů, působí jako antagonista CGRP receptoru. Vzhledem k rozdílnému mechanismu účinku může být účinným řešením pro pacienty, kteří nereagují na tradiční léčbu triptany nebo kteří triptany netolerují. Je prvním lékem, který má duální využití. Lze ho použít k terapii migrenózní ataky, zároveň je vhodný i pro preventivní léčbu, v této indikaci však úhradu stanovenu nemá. Rimegepant má příznivý bezpečnostní profil, během jeho užívání nebyla pozorována hepatotoxicita ani kardiotoxicita, nemá ani vazokonstrikční potenciál. Míra výskytu nežádoucích účinků je nízká a ve většině případů se jednalo o mírné nebo středně závažné nežádoucí účinky. Možnost širšího použití rimegepantu v klinické praxi díky jeho schválené úhradě posouvá standardy moderní péče o pacienty s migrénou.
Migraine is a common neurological disorder that affects a significant portion of the global population. The possibilities of its treatment in the Czech Republic have recently been enriched by the approval of reimbursement for rimegepant in the context of acute migraine treatment. Rimegepant, a drug from the gepant group, acts as a CGRP receptor antagonist. Due to its different mechanism of action, it can be an effective solution for patients who do not respond to traditional triptan treatments or who cannot tolerate triptans. It is the first medication with dual use, suitable for treating migraine attacks and also for preventive treatment; however, reimbursement has not yet been established for the latter indication. Rimegepant has a favorable safety profile, with no observed hepatotoxicity or cardiotoxicity, and it does not have vasoconstrictive potential. The frequency of side effects is low, most of them being mild to moderate. The broader use of rimegepant in clinical practice, enabled by its approved reimbursement, advances the standards of modern care for patients with migraine.
