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Background/Objectives: Sepsis is characterized by a dysregulated immune response to infection and is associated with high lethality. Extracellular DNA (ecDNA) has drawn significant interest as a damage-associated molecular pattern because of its potential involvement in the pathophysiology of sepsis. Methods: In this study, we examined the ecDNA concentration in 27 adult patients admitted to the intensive care unit. Fluorometry and quantitative PCR were used for the assessment of ecDNA. In addition, deoxyribonuclease activity was measured as a potential modulator of ecDNA. Results: Our findings reveal nearly 5-fold higher concentrations of ecDNA in non-survivors, suggesting its potential as a prognostic indicator for sepsis outcomes on day 7. Interestingly, the subcellular origin of ecDNA was similar between patients diagnosed with systemic inflammatory response syndrome, sepsis, and septic shock. Deoxyribonuclease activity, implicated in the cleavage of ecDNA, was comparable across all patient groups. Conclusions: To establish the prognostic value of ecDNA as a biomarker, further investigations within a larger patient cohort are needed. Nevertheless, our results suggest that high ecDNA in sepsis patients represents a negative prognostic biomarker.

It is currently unknown why obesity leads in some patients to prediabetes and metabolic syndrome. Microinflammation potentially caused by extracellular DNA is supposed to be involved. The aim of this cross-sectional study in healthy mice was to analyze the association between plasma extracellular DNA and glucose metabolism. Fasting glycemia and insulin were measured in healthy adult female mice that subsequently underwent an oral glucose tolerance test. Indices of glucose metabolism and insulin sensitivity were calculated. DNA was isolated from plasma and quantified fluorometrically. Deoxyribonuclease (DNase) activity of plasma was measured using the single radial enzyme diffusion method. Fasting glycemia correlated negatively with both, extracellular DNA and DNase (r = -0.44 and r = -0.32, respectively). DNase was associated positively with the incremental area under curve (r = 0.35), while extracellular DNA correlated negatively with total area under curve of glycemia during oral glucose tolerance test (r = -0.34). Measures of insulin sensitivity were found to be associated with neither extracellular DNA, nor DNase. The hypothesis of an association of low DNase with increased fasting glucose was partially proved. Surprisingly, low extracellular DNA is associated with higher fasting glucose and lower glucose tolerance in mice. As novel therapeutic targets for prediabetes and metabolic syndrome are highly needed, this study provides novel unexpected associations within the limitations of the focus on physiological variability as it was conducted on healthy mice. The causality of these associations should be proved in further interventional experiments.

Fever and hypothermia represent two opposite strategies for fighting systemic inflammation. Fever results in immune activation; hypothermia is associated with energy conservation. Systemic Inflammatory Response Syndrome (SIRS) remains a significant cause of mortality worldwide. SIRS can lead to a broad spectrum of clinical symptoms but importantly, patients can develop fever or hypothermia. During infection, polymorphonuclear cells (PMNs) such as neutrophils prevent pathogen dissemination through the formation of neutrophil extracellular traps (NETs) that ensnare and kill bacteria. However, when dysregulated, NETs also promote host tissue damage. Herein, we tested the hypothesis that temperature modulates NETs homeostasis in response to infection and inflammation. NETs formation was studied in response to infectious ( Escherichia coli , Staphylococcus aureus ) and sterile (mitochondria) agents. When compared to body temperature (37°C), NETs formation increased at 40°C; interestingly, the response was stunted at 35°C and 42°C. While CD16+ CD49d+ PMNs represent a small proportion of the neutrophil population, they formed ~45-85% of NETs irrespective of temperature. Temperature increased formyl peptide receptor 1 (FPR1) expression to a differential extent in CD16+ CD49d- vs . CD49d+ PMNSs, suggesting further complexity to neutrophil function in hypo/hyperthermic conditions. The capacity of NETs to induce Toll-like receptor 9 (TLR9)-mediated NF-κB activation was found to be temperature independent. Interestingly, NET degradation was enhanced at higher temperatures, which corresponded with greater plasma DNase activity in response to temperature increase. Collectively, our observations indicate that NETs formation and clearance are enhanced at 40°C whilst temperatures of 35°C and 42°C attenuate this response. Targeting PMN-driven immunity may represent new venues for intervention in pathological inflammation.

Deoxyribonucleases (DNases) cleave extracellular DNA (ecDNA) and are under intense research as interventions for diseases associated with high ecDNA, such as acute live injury. DNase I treatment decreases morbidity and mortality in this animal model. Endogenous DNase activity has high interindividual variability. In this study, we tested the hypothesis that high endogenous DNase activity is beneficial in an animal model of acute liver failure. DNase activity was measured in the plasma of adult male mice taken before i.p. injection of thioacetamide to induce acute liver failure. The survival of mice was monitored for 48 h. Mice were retrospectively divided into two groups based on the median DNase activity assessed using the gel-based single-radial enzyme diffusion assay. In acute liver failure, mice with a higher baseline DNase activity had lower mortality after 48 h (by 25%). Different protection of ecDNA against nucleases by vesicles or DNA-binding proteins could play a role and should be further evaluated. Similarly, the role of endogenous DNase activity should be analyzed in other disease models associated with high ecDNA.

Caffeine is well known for reducing fatigue and its effect on behavior is widely studied. Usually, caffeine is not ingested in its pure form but rather in sugar-sweetened beverages such as cola. Our aim was to compare the acute effect of cola and caffeine on locomotor activity. Rats and flies ingested cola or caffeine solution for 24 hours. The open field test revealed higher locomotor activity in cola groups for both flies and rats. Surprisingly, no differences have been observed between caffeine and control group. We conclude that caffeine itself does not explain the effect of cola on locomotor activity. Effect of cola cannot be generalized and interpreted for any caffeinated drink with other contents. Rather, the observed effect on locomotor activity may be caused by interaction of caffeine with other substances present in cola.

The soluble variant of the ectopeptidase CD13 (sCD13), released from the cell surface by matrix metalloproteinase 14 (MMP14), is a potent pro-inflammatory mediator, displaying chemotactic, angiogenic, and arthritogenic properties through bradykinin receptor B1 (B1R). We revealed a link between sCD13 and amplified neutrophil-mediated inflammatory responses in SARS-CoV-2 infection. sCD13 was markedly elevated in patients with COVID-19 and correlated with disease severity and variants, ethnicity, inflammation markers, and neutrophil extracellular trap formation (NETosis). Neutrophils treated with sCD13 showed heightened NETosis and chemotaxis, which were inhibited by sCD13 receptor blockade. Meanwhile sCD13 did not induce platelet aggregation. Single-cell analysis of COVID-19 lungs revealed coexpression of CD13 and MMP14 by various cell types, and higher CD13 expression compared with controls. Neutrophils with high CD13 mRNA were enriched for genes associated with immaturity, though CD13 protein expression was lower. Histological examination of COVID-19 lungs revealed CD13-positive leukocytes trapped in vessels with fibrin thrombi. Flow cytometry verified the presence of B1R and a second sCD13 receptor, protease-activated receptor 4, on monocytes and neutrophils. These findings identify sCD13 as a potential instigator of COVID-19–associated NETosis, potentiating vascular stress and thromboembolic complications. The potent pro-inflammatory effects of sCD13 may contribute to severe COVID-19, suggesting that sCD13 and its receptors might be therapeutic targets.

Wood, which is flammable, is commonly used as a building material and can be improved using a suitable surface treatment. A promising coating solution is polyurea, featuring properties like flexibility, mechanical resistance, resistance against water, etc., but it is also easily flammable. Expandable graphite (EG) is effective as a flame retardant and environmentally suitable. In this study, we studied the suitability of polyurea improved with EG. Spruce wood samples with dimensions of 50 mm × 40 mm × 10 mm were divided into eight groups, each including five samples. Each group was subjected to two applications of polyurea and EG in various combinations to examine the best combination with the lowest mass loss. The second component of the experiments aimed to examine the effectiveness of EG, which was applied in different weights. During the experiments, samples were thermally loaded in an apparatus for 10 min, where a heat flux of 30 kW·m−2 was applied to the sample surface and the mass loss was continuously recorded. Lastly, thermal analysis was performed. The best results were observed for the combination of NEOPROOF mixed with 0.3 g of EG covered with NEODUR. The thermal analysis results revealed substantial differences: NEOPROOF, a polyurea, had only one degradation step, while NEODUR, which also contained polyurethanes, decomposed in several steps.

Urinary tract infections (UTIs) are one of the most frequent infections in elderly people. The majority of infections is caused by uropathogenic E. coli. These strains contain a broad spectrum of virulence factors and are able to overcome defense barriers and colonize host organism. Population of elderly individuals has been growing globally and for that reason it is possible to expect a rise of UTIs among them. The aim of this study was to determine the phylogenetic group (A, B1, B2 and D) of urinary strains of E. coli isolated from elderly patients and evaluate the presence of 14 virulence genes ( hl y, cnf1, cdt, sat, afa, sfa, pap, aer, upaH, cah, pic, neuC, kpsMT II and traT) in these strains. We have carried out a phylogenetic analysis and virulence genes identification of 75 urinary E. coli isolates. Among our 75 E. coli strains, phylogenetic group B2 (64%) was the most dominant followed by groups D (16%), B1 (10.7%) and A (9.3%). The genes kpsMT II (65.3%), traT (61.3%), upaH (58.6%) and aer (52.0%) were found to be the most prevalent. We identified from 5 to 10 virulence genes in 44% strains belonging to B2 phylogroup. E. coli urinary strains examined in this study belonged mainly to phylogenetic group B2. We have also found that the majority of examined virulence genes, which are crucial for the establishment and maintenance of infection, were present in these strains.

Roma represent one of the largest and oldest minorities in Europe. Health of many of them, particularly those living in settlements, is heavily compromised by poor dwelling, low educational level, unemployment, and poverty rooted in generational poverty, segregation and discrimination. The cross-sectional population-based study using community based approach aimed to map the prevalence of viral hepatitis B/C and metabolic syndrome in the population living in separated and segregated Roma settlements and to compare it with the occurrence of the same health indicators in the majority population, considering selected risk and protective factors of these health indicators. The sample consisted of 452 Roma (mean age = 34.7; 35.2% men) and 403 non-Roma (mean age = 33.5; 45.9% men) respondents. Data were collected in 2011 via questionnaire, anthropometric measures and analysed blood and urine samples. A methodology used in the study as well as in the following scientific papers is described in the Methods section (i.e. study design, procedures, samples, methods including questionnaire, anthropometric measurements, physical measurements, blood and urine measurements). There are regions of declining prosperity due to high unemployment, long-term problems with poverty and depleted resources. Populations living in these areas, i.e. in Central and Eastern Europe in Roma settlements, are at risk of poverty, social exclusion and other factors affecting health. Therefore, we should look for successful long-term strategies and tools (e.g. Roma mediators, terrain work) in order to improve the future prospects of these minorities.

A total of 145 Escherichia coli strains causing pyelonephritis in children were investigated for the prevalence of genes encoding the following virulence factors (VFs): P fimbria (67.6 %), S fimbria (53.8 %), AFA adhesins (2.8 %), cytotoxic necrotizing factor 1 (37.9 %), α-hemolysin (41.4 %), and aerobactin (71.7 %). One hundred and thirty-six (93.8 %) isolates harbored at least one of the virulence genes detected in the present study. Statistically significant co-occurrent presence of two VF genes was found for α-hly–cnf1, α-hly–sfa, cnf1–sfa (p < 0.001), and α-hly–pap (p = 0.001). Twenty-six profiles of VF genes were detected in this study. The combinations of aer–pap and aer–pap–sfa–α-hly–cnf1 were presented with the highest frequency—both of them in 28 isolates (19.3 %). All E. coli strains included in the study were susceptible to meropenem, amikacin, and tobramycin; the highest frequency resistance was found toward ampicillin (43.4 %), piperacillin (31.7 %), tetracycline (15.9 %), and trimethoprim/sulfamethoxazole (11.7 %). The resistance to the other tested antimicrobial drugs did not exceed 3 % incidence. Overall, 55.9 % strains were susceptible to all tested anti-infective agents. Antimicrobial resistance of E. coli strains toward trimethoprim/sulfamethoxazole statistically significantly correlated with the presence of α-hly (p < 0.001), sfa (p < 0.01), and cnf1 (p < 0.05).