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Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression., (© 2023. Springer Nature Limited.)

Background: The NR3C2 gene encodes the mineralocorticoid receptor, which is present on cardiomyocytes. Prior studies reported an association between the presence of NR3C2 single-nucleotide polymorphisms (SNPs) and an increased cortisol production during a stress response such as acute myocardial infarction (AMI), which may lead to adverse cardiac remodeling. Objective: To study the impact of the NR3C2 rs2070950, rs4635799 and rs5522 gene polymorphisms on left ventricular (LV) remodeling, rhythm and conduction disorders in AMI patients. Methods: A cohort of 301 AMI patients who underwent revascularization was included. SNPs of the NR3C2 gene (rs2070950, rs4635799 and rs5522) were evaluated. A total of 127 AMI patients underwent transthoracic echocardiography follow-up after 72 h and 6 months. Results: The rs2070950 GG genotype and rs4635799 TT genotype were most common in patients who had LV end-diastolic volume increase < 20% and the same or increased LV ejection fraction, indicating a possible protective effect of these SNPs. The rs5522 TT genotype was associated with a higher frequency of arrhythmias, while the presence of at least one rs5522 C allele was associated with a lower risk of arrhythmias. Conclusion: SNPs of the NR3C2 gene appear to correlate with better ventricular remodeling and a reduced rate of arrhythmias post-AMI, possibly by limiting the deleterious effects of cortisol on cardiomyocytes.

Metal-based nanoparticles with antimicrobial activity are gaining a lot of attention in recent years due to the increased antibiotics resistance. The development and the pathogenesis of oral diseases are usually associated with the formation of bacteria biofilms on the surfaces; therefore, it is crucial to investigate the materials and their properties that would reduce bacterial attachment and biofilm formation. This work provides a systematic investigation of the physical-chemical properties and the antibacterial activity of TiO 2 thin films decorated by Ag and Au nanoparticles (NP) against Veillonella parvula and Neisseria sicca species associated with oral diseases. TiO 2 thin films were formed using reactive magnetron sputtering by obtaining as-deposited amorphous and crystalline TiO 2 thin films after annealing. Au and Ag NP were formed using a two-step process: magnetron sputtering of thin metal films and solid-state dewetting. The surface properties and crystallographic nature of TiO 2 /NP structures were investigated by SEM, XPS, XRD, and optical microscopy. It was found that the higher thickness of Au and Ag thin films results in the formation of the enlarged NPs and increased distance between them, influencing the antibacterial activity of the formed structures. TiO 2 surface with AgNP exhibited higher antibacterial efficiency than Au nanostructured titania surfaces and effectively reduced the concentration of the bacteria. The process of the observation and identification of the presence of bacteria using the deep learning technique was realized.

Background: Evidence shows that microRNAs (miRNAs) could play a key role in the homeostasis and development of major depressive disorder and bipolar disorder. The present study is aimed at investigating the changes in circulating miRNA expression profiles in a plasma of patients suffering from major depressive disorder (MDD) and bipolar disorder (BD) to distinguish and evaluate these molecules as biomarkers for mood disorders., Methods: A study enrolled a total of 184 subjects: 74 controls, 84 MDD patients, and 26 BD patients. Small RNA sequencing revealed 11 deregulated circulating miRNAs in MDD and BD plasma, of which expression of 5, hsa-miR-139-3p, miRNAs hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-125a-5p, and hsa-miR-483-5p, were further verified using qPCR. miRNA gene expression data was evaluated alongside the data from clinical assessment questionnaires., Results: hsa-let-7e-5p and hsa-miR-125a-5p were both confirmed upregulated: 0.75-fold and 0.25-fold, respectively, in the MDD group as well as 1.36-fold and 0.68-fold in the BD group. Receiver operating curve (ROC) analysis showed mediocre diagnostic sensitivity and specificity of both hsa-let-7e-5p and hsa-miR-125a-5p with approximate area under the curve (AOC) of 0.66. ROC analysis of combined miRNA and clinical assessment data showed that hsa-let-7e-5p and hsa-miR-125a-5p testing could improve MDD and BD diagnostic accuracy by approximately 10%., Conclusions: Circulating hsa-let-7e-5 and hsa-miR-125a-5p could serve as additional peripheral biomarkers for mood disorders; however, suicidal ideation remains the major diagnostic factor for MDD and BD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Dovydas Gecys et al.)

Background and Objectives : Serum cortisol has been extensively studied for its role during acute myocardial infarction (AMI). Reports have been inconsistent, with high and low serum cortisol associated with various clinical outcomes. Several publications claim to have developed methods to evaluate cortisol activity by using elements of complete blood count with its differential. This study aims to compare the prognostic value of the cortisol index of Endobiogeny with serum cortisol in AMI patients, and to identify if the risk of mortality in AMI patients can be more precisely assessed by using both troponin I and cortisol index than troponin I alone. Materials and methods : This prospective study included 123 consecutive patients diagnosed with AMI. Diagnostic coronary angiography and revascularization was performed for all patients. Cortisol index was measured on admission, on discharge, and after 6 months. Two year follow-up for all patients was obtained. Results : Our study shows cortisol index peaks at 7-12 h after the onset of AMI, while serum cortisol peaked within 3 h from the onset of AMI. The cortisol index is elevated at admission, then significantly decreases at discharge; furthermore, the decline to its bottom most at 6 months is observed with mean values being constantly elevated. The cortisol index on admission correlated with 24-month mortality. We established combined cut-off values of cortisol index on admission > 100 and troponin I > 1.56 μg/las a prognosticator of poor outcomes for the 24-month period. Conclusions : The cortisol index derived from the global living systems theory of Endobiogeny is more predictive of mortality than serum cortisol. Moreover, a combined assessment of cortisol index and Troponin I during AMI offers more accurate risk stratification of mortality risk than troponin alone.

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 years.

Objectives: Recently, genome-wide associated studies have identified several genetic loci that are associated with elevated blood pressure and could play a critical role in intracellular calcium homeostasis. The aim of this study was to assess the associations of ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms with high blood pressure (HBP) among Lithuanian children and adolescents aged 12-15 years., Study Design and Participants: This was a cross-sectional study of a randomly selected sample of 646 12-15-year-old adolescents who participated in the survey 'The Prevalence and Risk Factors of HBP in 12-15 Year-Old Lithuanian Children and Adolescents (from November 2010 to April 2012)'. Anthropometric parameters and BP were measured. The participants with HBP were screened on two separate occasions. Subjects were genotyped ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms using real-time PCR method., Results: The prevalence of HBP was 36.7%, significantly higher for boys than for girls. In the multivariate analysis, after adjustment for body mass index and waist circumference, boys with CACNB2 CG genotype, CACNB2 GG genotype and CACNB2 CG +GG genotype had higher odds of having HBP in codominant (adjusted OR (aOR)=1.92; 95% CI 1.16 to 3.18, p=0.011; and aOR=2.64; 95% CI 1.19 to 5.90, p=0.018) and in dominant (aOR=2.05; 95% CI 1.27 to 3.30, p=0.003) inheritance models. Girls carrying CACNB2 CG genotype and CACNB2 CG +GG genotype had increased odds of HBP in codominant (aOR=1.82; 95% CI 1.02 to 3.24, p=0.044) and in dominant (aOR=1.89; 95% CI 1.09 to 3.28, p=0.023) inheritance models. Furthermore, significant associations were found in additive models separately for boys (aOR=1.72; 95% CI 1.20 to 2.46, p=0.003) and girls (aOR=1.52; 95% CI 1.05 to 2.20, p=0.027). No significant association was found between ATP2B1 gene polymorphism and the odds of HBP., Conclusions: Our results indicate that CACNB2 gene polymorphism was significantly associated with higher odds of HBP in Lithuanian adolescents aged 12-15 years., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To examine the MMP-2 (-1306 C/T) gene polymorphism and the phenotype characterized by soft and hard drusen of early age-related macular degeneration (AMD) and geographic atrophy of late AMD form., Methods: The study enrolled 850 investigations (290 AMD patients with soft and hard drusen, 34 with geographic atrophy and a random sample of the population n =526). Early AMD was classified according to the International Classification and Grading System. For geographic atrophy diagnosis the Age-Related Eye Disease Study classification was used. The potential association with single nucleotide polymorphisms on MMP-2 Rs243865 was evaluated for all patients, adjusted for age and sex. The genotyping test of MMP-2 Rs243865 (C-->T) was conducted using the real-time polymerase chain reaction method., Results: MMP-2 (-1306 C/T) C/C genotype was more frequently detected in AMD patients with hard drusen than the soft drusen or control group (66.43% vs 53.74%, vs 54.94%, P =0.047). Logistic regression analysis showed that the MMP-2 (-1306) C/C genotype increased the likelihood to develop hard drusen in AMD patients (OR=1.7, 95% CI: 1.06-2.74; P =0.028). No association between MMP-2 (-1306 C/T) gene polymorphism in patients with atrophic AMD and control group was found (54.94%, 37.64%, 7.41% vs 50%, 38.24%, 11.76%; P =0.6)., Conclusion: The MMP-2 Rs24386 (C-->T) polymorphism is found to be associated with the development of hard drusen in patients with AMD.

Background: Epidemiological studies have demonstrated the influence of environmental factors on HBP in the population of Lithuanian children, although the role of genetic factors in hypertension has not yet been studied. The aim of this study was to assess the distribution of AGTR1, AGT, and ACE genotypes in the Lithuanian child population and to determine whether these genotypes have an impact on HBP in childhood., Methods: This cross-sectional study enrolled 709 participants aged 12-15 years. The subjects were genotyped for AGT (M235 T, rs699), AGTR1 (A1166C, rs5186), and ACE (rs4340) gene polymorphisms using real-time and conventional polymerase chain reactions. Blood pressure and anthropometric parameters were measured., Results: The prevalence of HBP was 38.6% and was more frequently detected in boys than in girls (47.9% vs. 29.5%; p < 0.001). No significant differences in the frequencies of the AGT or AGTR1 genotypes or alleles between boys and girls were observed, except for ACE genotypes. The mean SBP value was higher in HBP subjects with ACE ID genotype compared to those with ACE II homozygotes (p = 0.04). No significant differences in BP between different AGT and AGTR1 genotype groups were found. Boys who carried the ACE ID + DD genotypes had higher odds of having HBP than carriers of the ACE II genotype did (controlling for the body mass index (BMI): OR MH  = 1.83; 95% CI, 1.11-3.02, p = 0.024; and controlling for waist circumference (WC): OR MH  = 1.76; 95% CI, 1.07-2.92, p = 0.035). These associations were not significant among girls. The same trend was observed in the multivariate analysis - after adjustment for BMI and WC, only boys with ACE ID genotype and ACE ID + DD genotypes had statistically significantly increased odds of HBP (aOR = 2.05; 95% CI, 1.19-3.53 (p = 0.01) and aOR = 1.82; 95% CI, 1.09-3.04 (p = 0.022), respectively)., Conclusions: The evaluated polymorphisms of the AGT and AGTR1 genes did not contribute to the presence of HBP in the present study and may be seen as predisposing factors, while ACE ID genotypes were associated with significantly increased odds for the development of HBP in the Lithuanian child and adolescent population - especially in boys.

Background: The roots of adult hypertension go back to childhood. This study aimed to examine the independent effects of physical, behavioural and genetic factors identified in childhood and mid-adulthood for prediction of adult hypertension., Methods: The study subjects were participants of the Kaunas Cardiovascular Risk Cohort study started in 1977 (n = 1082, age 12-13 years). In 2012, a total of 507 individuals (63.9% of eligible sample) participated in the 35-year follow-up survey. Health examination involved measurements of blood pressure (BP), anthropometric parameters, and interview about health behaviours. Subjects were genotyped for AGT (M235T), ACE (I/D, rs4340), ADM (rs7129220), and CACNB2 (rs12258967) genes polymorphisms. A genetic risk score was calculated as the sum of the number of risk alleles at each of four single nucleotide polymorphisms., Results: AGT TT genotype male carriers had the highest mean values of systolic BP in childhood. In females, ADM genotype AA was associated with the highest values of systolic and diastolic BP, while CACNB2 genotype CC carriers had the highest values of diastolic BP in childhood. Systolic and diastolic BP in childhood, gain in BMI from childhood to adulthood, and risky alcohol consumption predicted hypertension in middle-aged men. In women, genetic risk score together with diastolic BP in childhood and gain in BMI were significant predictors of adult hypertension. The comparison of four nested logistic regression models showed that the prediction of hypertension improved significantly after the addition of BMI gain. Genetic risk score had a relatively weak effect on the improvement of the model performance in women., Conclusions: BP in childhood and the gain in BMI from childhood to adulthood were significant predictors of adult hypertension in both genders. Genetic risk score in women and risky alcohol consumption in men were independently related with the risk of adult hypertension.

Introduction: The development of left ventricular remodelling after acute myocardial infarction is a predictor of heart failure and mortality. The purpose of the present study was to assess whether the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) had effects on cardiac remodelling after acute myocardial infarction., Methods: One hundred and forty-one patients (mean age 56.4±11.1 years) with a first acute myocardial infarction were enrolled. Within 24-72 hours of the onset of the symptoms and at a four month period two-dimensional echocardiography was performed. Remodelling was defined as a 20% increase from the baseline in left ventricular end-diastolic volume. The genotypes of the study group were compared with the reference group (n=1010) genotypes. AGT M235T polymorphism was determined using polymerase chain reaction amplification., Results: At follow-up, 49 patients (34.7%) were classified as having left ventricular remodelling. Anterior localization of the infarct (p=0.008), leucocyte count at admission (p=0.040), global left ventricular longitudinal strain (p=0.021) and MM genotype of AGT (p=0.024) were independent predictors of ventricular remodelling after myocardial infarction., Conclusions: Anterior wall infarction, increased leucocyte count, decreased longitudinal strain of left ventricular and polymorphism of AGT M235T may predict remodelling after myocardial infarction., (© The Author(s) 2013.)

Matrix metalloproteinase-3 (MMP-3) degrades extracellular matrix and may lead to development of dilatative pathology of ascending thoracic aorta. Expression of MMP-3 depends upon the 5A/6A polymorphism in the promoter region. An increased number of 5A alleles leads to high expression of MMP-3. Thus, objective of the study was to determine whether the 5A/6A polymorphism in the promoter region of MMP-3 gene is associated with the development of dilatative pathology of ascending thoracic aorta. We studied 76 patients (age ranged from 31 to 81 years; median age, 64 years) who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n=604) aged 25-64 years, all from Lithuania. DNA was analyzed by using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position -1171 of the MMP3 gene promoter. The prevalence of MMP-3 genotypes was similar in the group of dilatative pathology of ascending thoracic aorta and random sample of population. The frequency of 5A allele did not differ significantly between both groups and was 0.506 and 0.514, respectively. Male carriers of 5A/5A genotype were significantly younger compared with those with the 6A/6A genotype. In conclusion, the frequency of MMP-3 promoter 5A/6A genotypes did not differ between the group of patients with dilatative pathology of ascending thoracic aorta and the random sample of population, but the males with dilatative pathology of ascending thoracic aorta and 5A/5A genotype required aortic reconstruction surgery at the younger age than the males carrying 6A/6A genotype in the MMP-3 promoter region.

Unlabelled: The objective of this study was to examine the effect of chronic exposure to cadmium and zinc on the mice resistance to experimental Listeria monocytogenes infection., Materials and Methods: At the day beginning of experiment outbred mice were injected with suspension of bacteria and 8 weeks were given the following oral intake treatment: control group (n=28) deionized drinking water, Cd- group (n=37) water containing CdCl2 10 mg/l and Cd+Zn- group (n=33) water containing CdCl2 10 mg/l and ZnSO4 100 mg/l. The delayed type hypersensitivity was evaluated by the inflammatory response during so-called "foot" test. Listerial proteins solution was injected under plantare of lower aponeurosis of rear foot of experimental animals. Survival of L. monocytogenes in organs of experimental animals was evaluated by the presence of bacteria colonies after 30 days incubation of livers homogenates in broth medium at +4 degrees C and inoculation on CASO-agar. Kidneys, liver and spleen were used for metals analysis. Differences were significant if the P value was below 0.05., Results: Chronic exposure to Cd or to Cd with Zn for 8 weeks caused influence on survival of mice: Cd- and Cd+Zn groups mice died more rapidly than control group ones. Bacterial growth in organs was observed for all groups until fourth week. From sixth-week, control and Cd+Zn- group's mice more rapidly eliminated bacteria from organs, demonstrating that Zn- treated mice were more resistant to listerial infection than Cd- intoxicated ones. On the other hand, mice from Cd+Zn- group had significantly decreased spleen index (up to 74%, p<0.01) as compared to control group. Chronic poisoning of mice with low doses cadmium and zinc during infection significantly affected (p<0.05) their growth rate from fourth week in both experimental groups. Cadmium and zinc insignificantly decreased the delayed type hypersensitivity response to L. monocytogenes allergens in Cd+Zn- group of mice, and no differences were observed in Cd- group, as compared with control group., Conclusions: 1. Cadmium-exposed mice are more susceptible to Listeria monocytogenes and to other opportunistic infections than not intoxicated mice. 2. Zinc significantly reduces the negative effect of cadmium on the antimicrobial defense of mice. 3. Cadmium and zinc no significantly decrease the delayed type hypersensitivity response to L. monocytogenes allergens as compared with control.

Impact of aluminium ions on the translation process in mice liver, kidney, skeletal muscle and heart was investigated in vivo as well as on the protein synthesis in liver cell-free translation system in vitro. We find that at early stages of intoxication the effect of aluminium ions on protein synthesis in muscle tissues differs qualitatively from that one in liver or kidneys. Most noticeable aluminium-induced changes of protein synthesis in organs in vivo occur within the first 15-20 h after intoxication. We show that aluminium ions activates protein synthesis in liver and kidneys (at 8-16 h) while in skeletal muscle and heart does not. These results indirectly are supported by the data of experiments in vitro, which demonstrate that at low concentration aluminium ions activates protein synthesis in the cell-free translation system prepared from liver.

This study presents evaluation of effects of aluminium ions on the development of experimental infection induced by the injection of Listeria monocytogenes bacteria into growing mice. We show that single exposure of mice to 0.05 LD50 or 0.5 LD50 of aluminium ions does not affect the accumulation of bacteria in liver and spleen of experimental animals. Long-term exposure of mice to aluminium ions (injection of 0.05 LD50 Al3+ every 3 days for totally 6 weeks) did not slow down the increase in weight of animals while in the infected animals aluminium significantly reduced their growth. Animals subjected to chronic aluminium exposure have shown lower accumulation of bacteria in liver 24 h after the initiation of experimental infection as compared to the mice after single injection of 0.05 LD50 Al3+. Also, long-term exposure to aluminium causes more complicated development of experimental infection, which was evidenced by the decreased survival of aluminium-treated animals (77% compared to 83% in control group) as well as by the increase in the fraction of animals carrying infection after 6 weeks (36% versus 5% in control group). In addition, aluminium-exposed animals had significantly lower blood serum agglutination titer to the listeria, and decrease in the delayed type of hypersensitivity to the listeria antigens. Results, presented here, indicate that the long-term exposure to low aluminium doses activates the antibacterial defence in experimental animals while the specific immunity becomes suppressed.