Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions.

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers

Morphogenesis of thoracic aorta aneurysms: investigation of matrix metalloproteinases and their tissue inhibitors

The matrix metalloproteinases are a large group of proteases with a central role of the degradation of all types of extracellular matrix. The present study investigated expression of matrix metalloproteinases (MMP-1, -2, -9) and their inhibitors (TIMP-1, -2) in chronic Aneurysm of the Thoracic Aorta (ATA) and Post-Stenotic Dilatation of the ascending aorta due to valvular aortic stenosis (PSD). Fragments of the ascending aorta that had been taken from the patients during coronary by-pass surgery were used as controls. Immunohistochemical investigation showed that medial SMC in the samples taken from aortas with ATA and PDS expressed a stronger immunoreactivity for MMP-1, -2 , -9 and TIMP-1, -2 as compared to controls. It can be suggested that during formation of ATA and PSD, production of MMPs and TIMPS by medial smooth muscle cells is of great importance

Programmed cell death: molecular mechanisms and detection

Apoptosis or programmed cell death is genetically determined process to destroy cells for the maintaining of cellular homeostasis in the tissue. This paper reviews the current knowledge on the molecular mechanisms of apoptosis. Activation of cystein proteases called caspases plays a major role in the execution of apoptosis. These activated caspases selectively cleave cellular proteins, which result in apoptotic morphology (internucleosomal fragmentation of DNA into 180-200 base pair pieces, shrinkage of the cell and the nucleus as well and fragmentation of the cell into apoptotic bodies) and death of the cell. Now two pathways of caspase activation are reporteted. The first through triggering of cellular death-receptor superfamily. The second is mitochondrial pathway induced by the changes of the expression of pro- and anti-apototic genes in the cell. It leads to release of cytochrome c and apoptosis inducing factor from mitochondria. The paper reviews also currently used methods of detection of apoptotic cells in tissue samples, causes of false-positive or false-negative results of ISEL and TUNEL in situ reactions

Expression of matrix metalloproteinases (MMP-2 and MMP-9) in vocal fold polyps

Objective. Vocal fold polyps are the most common benign laryngeal lesions. Matrix metalloproteinases (MMP) play an important role in the physiological and pathological remodeling of tissues. The most important subgroup of MMP family consists of gelatinases A and B (MMP-2 and MMP-9). The objective of this study was investigation of the expression of MMP-2 and MMP-9 in vocal fold polyps and normal tissue of vocal folds. Material and methods. The immunohistochemical expression of MMP-2 and MMP-9 was investigated in specimens taken by endolaryngeal microsurgery from vocal fold polyps (n=30) and normal tissue of vocal fold (n=13, control group). Expression of MMP-2 and MMP-9, both in epithelium and stroma cells, was graded on a semiquantitative scale, ranging from 0 (no expression) to 6 points (high expression). Results. A statistically significant increase was observed in the expression of MMP-2 in stroma cells (P=0.0176) of vocal fold polyps compared to control vocal fold group, whereas no significant difference in the expression of MMP-2 was found in epithelium cells (P=0.1487). Comparison of expression of MMP-2 and MMP-9 in epithelium cells revealed a statistically significant increase in MMP-9 expression (P<0.01) in both groups. However, there was no statistically significant difference in the expression of MMP-9 between groups of vocal fold polyps and control vocal folds. Conclusion. Expression of MMP-2 in stroma was significantly higher in polyps than in normal tissue of vocal folds. Our data draw attention to the role of MMP-2 in the development of vocal fold polyps and necessity of further investigations to define its function in morphogenesis of laryngeal benign, premalignant, and malignant lesions

Ankylosing Spondyloarthritis Resulting Severe Aortic Insufficiency and Aortitis: Exacerbation of Ankylosing Spondyloarthritis and Stenosis of the Main Left Coronary Artery after Mechanical Aortic Valve Implantation with Cardiopulmonary Bypass

Ankylosing spondyloarthritis (AS) is a chronic inflammatory rheumatic disease, strongly related to human leukocyte antigen (HLA)-B27. Cardiac involvement in AS manifests in 2 to 10% of patients as aortic insufficiency, aortitis, mitral valve fibrosis, or disturbance in the conduction of the heart. In this article, we present a case of a 49-year-old male patient with AS, who was referred to our medical institution for elective aortic valve surgery because of severe aortic regurgitation. The histological findings revealed fibrosing endocarditis of aortic valve and nonspecific aortitis of aortic root. Late postoperatively, we observed exacerbation of AS and narrowing of the main left coronary artery (LAD). Our case highlights the importance of proper treatment of AS before and after cardiac surgery. Furthermore, in this case, we suspect association between cardiopulmonary bypass, activity of AS, and coronary artery disease

Association between genetic variants and obesity in the Lithuanian adult population

Introduction: Eating habits play a big role in the onset of obesity and there are some genes, associated with regulation of the food intake. The melanocortin-4 receptor (MC4R) and neuropeptide Y (NPY) are peptides that play part in the hypothalamic appetite regulation mechanism. Fat mass and obesity associated (FTO) gene variant is associated with human adiposity and metabolic disorders. The aim of this study was to evaluate the effect of MC4R, NPY and FTO genes polymorphisms on body mass index in the Lithuanian adult population. Methods: The study subjects were participants of the Kaunas Cardiovascular Risk Cohort study. The data from 507 subjects (48-49 year-old) were analysed. The single-nucleotide polymorphisms, MC4R rs17782313, NPY rs16139, FTO rs9939609 gene was assessed using a real-time polymerase chain reaction. Results: We found that the MC4R rs17782313 polymorphism has a statistically significant effect on the body mass index in the Lithuanian population: women with the CT and CC genotypes have a higher BMI by 1,97 kg/m 2 than women with the TT genotype, men with the same genotype have a 1,53kg/m 2 higher BMI than men with the TT genotype. The carriers of the FTO AA genotype had the highest mean values of body mass index. (BMI). They had 1.72 time higher odds of obesity (P=0.009) than those with the TT genotype. We didn‘t find statistically significant association between the NPY rs16139 polymorphism and BMI. Conclusion: The MC4R rs17782313 and FTO rs9939609 variants were significantly associated with BMI, and with the risk of obesity in the Lithuanian population

Associations of the adrenomedullin gene polymorphism with prehypertension and hypertension in Lithuanian children and adolescents: a cross-sectional study

The aim of this study was to evaluate the association of ADM genetic variant and HBP among Lithuanian adolescents aged 12-15 years. This is a cross-sectional study of a randomly selected sample of 675 12-15-years-old schoolchildren who were surveyed during November 2010 to April 2012 in the baseline survey. Single-nucleotide polymorphism (SNP) of ADM gene (rs7129220) was evaluated using real-time PCR. Logistic regression analyses were used to test the associations of ADM (rs7129220) polymorphism with HBP under four inheritance models based on the Akaike Information Criterion (AIC) and to calculate the odds ratios. In the multivariate analysis, boys carrying ADM AG genotype (vs. carriers of ADM GG genotype), ADM AG + AA genotype (vs. carriers of ADM GG genotype) and ADM AG genotype (vs. carriers of ADM GG + AA genotype) had higher odds of having hypertension in codominant, dominant, and overdominant inheritance models. Girls with ADM AG + AA had increased odds of prehypertension compared to girls with the ADM GG genotype carriers in dominant inheritance model. Significant associations were observed in additive models separately for boys (hypertension) and girls (prehypertension). Our results indicate that ADM gene polymorphism was significantly associated with higher odds of HBP in Lithuanian adolescents aged 12-15 year

Long Noncoding RNAs CARMN, LUCAT1, SMILR, and MALAT1 in Thoracic Aortic Aneurysm: Validation of Biomarkers in Clinical Samples

Background and Objectives. Thoracic aortic aneurysm (TAA) is a silent disease characterised by aortic wall expansion and vascular smooth muscle cell (VSMC) dedifferentiation from contractile to synthetic phenotype. Long noncoding RNAs (lncRNAs) involved in VSMC phenotypic regulation could be considered as potential diagnostic indicators and therapeutic targets of TAA. In vitro studies show that lncRNAs CARMN, LUCAT1, MALAT1, and SMILR are associated with the VSMC phenotypic state. Our aim was to test if these lncRNAs are dysregulated during TAA formation in clinical patient samples. Materials and Methods. Relative expression of lncRNAs CARMN, LUCAT1, SMILR, and MALAT1 was tested in clinical aortic tissue and blood plasma samples from TAA and non-TAA patients using the qRT-PCR method. The Mann–Whitney U test was used to compare ΔCt values between the study groups. ROC curve analysis was performed to evaluate the diagnostic value of plasma lncRNAs. Results. We found significantly reduced CARMN (p = 0:033) and LUCAT1 (p = 0:009) expression in aortic tissue samples from TAA patients. Relative expression of MALAT1 (p = 0:117) and SMILR (p = 0:610) did not differ in aortic tissue between the TAA and non-TAA groups. Expression of both LUCAT1 and SMILR was significantly decreased in TAA patients’ blood plasma compared to controls (p = 0:018 and p = 0:032, respectively). However, only LUCAT1 showed the ability to discriminate aneurysmal disease in patients’ blood plasma (AUC = 0:654, 95%CI = 0:534‐0:775, p = 0:018). Conclusions. We have shown that the expression of lncRNAs CARMN and LUCAT1 is reduced in dilated aortic tissue and that the LUCAT1 and SMILR expression is lower in the blood plasma of TAA patients. Decreased LUCAT1 expression in TAA patients’ blood plasma may have diagnostic potential in discriminating patients with TAA

Matrix metalloproteinases (MMP-2,-3,-9) gene polymorphisms in cases of benign vocal fold lesions and laryngeal carcinoma

BACKGROUND/AIM: The matrix metalloproteinases (MMP) play an important role in the physiological and pathological remodeling of tissues including carcinogenesis. The study's aim was to assess the relations between MMP-2(-735C/T), MMP-2(-1306C/T), MMP-9(-1562C/T), and MMP-3(-11715A/6A) polymorphisms, and clinical/morphological manifestation of laryngeal squamous cell carcinoma (LSCC) and benign vocal fold lesions (BVFL). PATIENTS AND METHODS: Two hundred and seventeen patients with LSCC and BVFL and 458 controls were included in this study. The genotyping was performed using the real-time polymerase chain reaction method. RESULTS: The MMP-2(-1306C/T) C/T genotype was significantly rarer among the patients with moderate-poorly differentiated LSCC compared to the control group, however the MMP-3(-11715A/6A) 6A/6A genotype was significantly more frequent compared to controls. Smoking and 6A/6A genotype of MMP-3(-11715A/6A) polymorphism were associated with increased odds of LSCC risk. No associations between MMP genotypes and BVFL were found. CONCLUSION: Smoking and MMP-3 (-11715A/6A) 6A/6A genotype may cause a higher risk for developing LSCC

The Impact of CYP4F2 rs3093135 TT variant on bleeding and thrombosis in dual antiplatelet therapy users

Introduction: Dual antiplatelet therapy (DAPT) of thienopyridines (ticagrelor or clopidogrel) and aspirin is recommended for patients with acute coronary syndromes for a period of 12 months after percutaneous coronary intervention (PCI) and stent implantation. Individual patients` genetic and non-genetic factors may determine bleeding and thrombosis during DAPT. As it was showed already, CYP4F2 rs2108622 may significantly affect antiplatelet treatment with clopidogrel. Our most recent data showed, that CYP4F2 rs3093135 TT variant carriers, users of ticagrelor, had lower platelet aggregation values than non-carriers. Aim: To determine the impact of CYP4F2 rs3093135 TT variant on bleeding and trombosis in patients treated with dual thienopyridine (ticagrelor or clopidogrel) and aspirin antiplatelet therapy after percutaneous coronary intervention (PCI) and stent implantation. Methods: This prospective study was carried out with the patients hospitalized with acute coronary syndromes at the Department of Cardiology of Hospital of Health Sciences, Lithuania between January 2013 till December 2016. All the patients received dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel and aspirin for at least of 6 months after PCI and stent implantation. From a total of (n=378) patients receiving DAPT, only the patients with CYP4F2 rs3093135 TT variant (n=33) were selected into this study. Bleeding was defined according to Bleeding Academic Research Consortium (BARC) classification. Results: From a total of 33 patients, carriers of CYP4F2 rs3093135 TT variant, 9 (27.3%) patients received ticagrelor and 24 (72.7%) were treated with clopidogrel. Only 2 patients who used ticagrelor had no bleeding events. Seven patients had type 1 or 2 bleeding according to BARC classification and one patient had a major type 3a gastrointestinal bleeding and required a blood tranfusion. The bleeding events were not documented in clop[...]