Early dynamics of glial fibrillary acidic protein and extracellular DNA in plasma of mice after closed head traumatic brain injury.

BACKGROUND: Glial fibrillary acidic protein (GFAP) in plasma is an established biomarker of traumatic brain injury (TBI) in humans. Plasma extracellular DNA (ecDNA) is a very sensitive, although nonspecific marker of tissue damage including TBI. Whether plasma GFAP or ecDNA could be used as an early non-invasive biomarker in the mouse model of closed head injury is unknown. The aim of this paper was to describe the early dynamics of plasma GFAP and ecDNA in the animal model of closed head TBI. METHODS: Closed head TBI was induced using the weight-drop method in 40 adult CD1 mice and blood was collected in different time points (1, 2 or 3h) after TBI in different groups of mice. Plasma GFAP and ecDNA and ecDNA fragmentation from the experimental groups were compared to healthy controls. In the surviving mice, a static rods test was performed 30 days after TBI to assess the neurological outcome of TBI. RESULTS: Despite a trend of higher plasma GFAP after TBI the differences between the groups were not statistically significant. Plasma ecDNA was higher by 50% after 1h (P<0.05) and 2h (P<0.05) after TBI and was highly variable after 3h. Plasma ecDNA, but not GFAP, was partially predictive of the neurological impairment of the mice. CONCLUSION: In this study, we have described the early dynamics of plasma GFAP and ecDNA after TBI in mice. According to our results, ecDNA in plasma is a more sensitive early marker of TBI than GFAP. Analysis of tissue-specific ecDNA might improve its predictive value regarding the survival and neurobehavioral outcome.

Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a long-term care facility during Covid-19 outbreak.

BACKGROUND: Covid-19 is a disease with high morbidity and mortality among elderly residents of long-term care facilities (LTCF). During an outbreak of SARS-CoV-2 infection in the LTCF an effective screening tool is essential to identify the patients at risk for severe disease. We explored the role of interleukin 6 (IL-6) as a predictor for severe disease during the outbreak of Covid-19 in one LTCF in Slovakia. METHODS: We conducted a retrospective data analysis of cases of COVID-19, diagnosed during the outbreak in one LTCF in Slovakia between April 11, 2020, and May 5, 2020. Within 24 h after the diagnosis of Covid-19, clinical and laboratory screening was performed in the LTCF to identify patients in need of hospitalization. Patients with oxygen saturation below 90% were immediately referred to the hospital. Patients staying in the LFTC were monitored daily and those that developed hypoxemia were transferred to the hospital. We analyzed the association between the IL-6 at the initial assessment and development of hypoxemia during follow up and determined the cut-off of the IL-6 able to predict the development of hypoxemia requiring oxygen therapy. RESULTS: Fifty-three patients (11 men, 42 women) with diagnosed Covid-19 were included in the analysis. 19 (53%) patients developed hypoxemia during the disease. Patients with hypoxemia had significantly higher concentrations of IL-6, C-reactive protein, procalcitonin, fibrinogen, total bilirubin, aspartate aminotransferase and alanine aminotransferase at initial screening. ROC analyses identified IL-6 as the most robust predictor of hypoxemia. The concentration of IL-6 > 24 pg/mL predicted the development of hypoxemia with the sensitivity of 100% and specificity of 88.9%. The positive and negative predictive values were 76.9, and 100% respectively. CONCLUSIONS: The concentration of IL-6 > 24 pg/mL at initial assessment predicted the development of hypoxemia requiring hospitalization with excellent sensitivity and good specificity. IL-6 appears as a potential predictor for the development of the severe Covid-19 and might serve for early identification of patients in need of hospitalization. Further studies are needed to evaluate the robustness of the use of IL-6 as an effective screening tool for the severe course of Covid-19.

Extracellular DNA is Increased in Dextran Sulphate Sodium-Induced Colitis in Mice.

Ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease. Prevalence of these diseases increases. In the present day, inadequate and inefficient therapy causes complications and frequent relapse. Extracellular DNA (ecDNA) is the DNA that is outside of cells and may be responsible for activation of the inflammatory response. To determine whether colitis is associated with higher concentration of ecDNA we used male mice of the C57BL/6 strain. Colitis was induced by 2% dextran sulphate sodium (DSS). After 7 days, mice exhibited considerable weight loss compared to the control group. Also, there was a higher stool consistency score and the colon was significantly shorter in comparison to the control group. Higher concentration of ecDNA was found in the DSS group. Interestingly, deoxyribonuclease activity was lower in the colon of the DSS group compared with the negative control. These findings may point to ecDNA as a potential pathogenetic factor and marker of inflammation.

Beneficial effects of live and dead Salmonella-based vector strain on the course of colitis in mice.

Dysbiosis of intestinal microbiota and hyperactive immune responses seem to be crucial for the uncontrolled inflammation in inflammatory bowel diseases (IBD). Modulation of the microbiome and immune stimulation of the intestinal epithelium were suggested as therapeutic approaches. In this study, live attenuated and dead bacterial cells of Salmonella Typhimurium SL7207 - a widely used bacterial vector for gene therapy were administered in DSS-induced colitis in mice. C57BL/6 mice were divided into four groups. The first group received pure water (CTRL). The other three groups received 2% dextran sulphate sodium (DSS) to induce colitis. Two DSS groups were treated with live attenuated (DSS live) or inactivated (DSS dead) Salmonella by gastric gavage. Intake of 2% DSS caused weight loss in all DSS groups compared to control mice with some improvement in DSS live group on the last day of the experiment. Significantly longer colon and improved stool consistency were reported in DSS live group, but not DSS dead group, when compared with DSS. Significant enlargement of spleens was observed only in DSS and DSS dead groups compared to control. Significant differences in stool consistency, colon length and spleen enlargement were observed between DSS live and DSS dead groups with beneficial effects of live bacteria. Interestingly, significant decrease in myeloperoxidase activity was detected in both, DSS live and DSS dead groups compared to the DSS group. On the basis of these results, progression of colitis seems to be beneficially influenced not only by live attenuated but to some extent also by inactivated Salmonella Typhimurium SL7207. Our results provide evidence that Salmonella-based gene therapy vectors are able to positively alter gut homeostasis during DSS-induced colitis. SIGNIFICANCE AND IMPACT OF THE STUDY: Restoration of gut homeostasis has a great importance in IBD. Here, we tested the nonspecific effect of the strain Salmonella Typhimurium SL7207 on the course of colitis to find out whether the potential effect would be mediated by activity of live bacterial cells or by bacterial structures that are also present in dead bacteria. Live bacterial therapy of colitis showed a beneficial effect on clinical signs as well as on macroscopic and inflammatory markers of colitis. On the other hand, therapy with dead bacteria showed inconsistent effects, negative in most clinical outcomes, positive especially in myeloperoxidase activity. Our data indicate that the beneficial effect of bacterial gene therapy vectors carrying therapeutic genes might be, at least partially, caused by the bacterial vector instead of the therapeutic gene.

Environmental photostability of SF6-etched silicon nanocrystals.

We report on the long-term environmental stability of the photoluminescent (PL) properties of silicon nanocrystals (SiNCs). We prepared sulfur hexafluoride (SF(6)) etched SiNCs in a two-stage plasma reactor and investigated their PL stability against UV irradiation in air. Unlike SiNCs with hydrogen-passivated surfaces, the SF(6)-etched SiNCs exhibit no photobleaching upon extended UV irradiation despite surface oxidation. Furthermore, the PL quantum yield also remains stable upon heating the SF(6)-etched SiNCs up to 160 °C. The observed thermal and UV stability of SF(6)-etched SiNCs combined with their PL quantum yields of up to ~50% make them attractive candidates for UV downshifting to enhance the efficiency of solar cells. Electron paramagnetic spin resonance indicates that the SF(6)-etched SiNCs have a lowered density of defect states, both as-formed and after room temperature oxidation in air.

SF6 plasma etching of silicon nanocrystals.

An SF(6)-based plasma has been employed to perform in-flight etching of silicon nanocrystals (Si-NCs) after they were synthesized in an SiH(4)-based plasma. The photoluminescence of the Si-NCs blue-shifts after etching, indicating an etching-induced size reduction of the Si-NCs. It is shown that both the SF(6) plasma power and the flow rate can be utilized to control the etch rate (and thus the size reduction) of the Si-NCs. The SF(6) etched Si-NCs show only low concentrations of residual impurities other than fluorine. Quantum yields as high as 50% have been observed from these SF(6) etched Si-NCs despite oxidation.

Air-stable full-visible-spectrum emission from silicon nanocrystals synthesized by an all-gas-phase plasma approach.

A novel dual-plasma system has been developed to combine the synthesis of silicon nanocrystals (Si-NCs), the etching to controllably tailor the Si-NC size, and the surface functionalization of Si-NCs into one simple all-gas-phase process. Si-NCs are synthesized in SiH(4)-based plasma; they then travel through CF(4)-based plasma, where Si-NCs are etched and passivated by C and F. The resulting Si-NCs exhibit air-stable emission across the full visible spectrum. Structural and optical characterization indicates that the emission in the red-to-green range is based on the recombination of quantum-confined excitons in Si-NCs, while the blue emission originates from defect states. The quantum yields of stabilized photoluminescence from Si-NCs range from 16% at the red end to 1% at the blue end.

Invincible Athletics program: aerobic exercise and performance without strain.

This study compared physiologic pattern during conventional aerobic exercise to those during Invincible Athletics--a program emphasizing balance and comfort during exercise to increase strength, endurance, and mind-body coordination gradually without the negative effects of the stress/recovery cycle. While heart rats were similar during both workouts, during Invincible Athletics: (1) perceived comfort tended to be higher and perceived exertion tended to be lower; (2) breath rates were significantly lower; (3) respiratory sinus arrhythmia and central-parietal alpha relative power were significantly higher; and (4) endurance was significantly longer. Respiratory sinus arrhythmia decreases with physiologic and mental stress. Heightened respiratory sinus arrhythmia and EEG alpha relative power along with subjective reports of greater comfort, less exertion, and observed increased endurance suggest that during Invincible Athletics athletes may be more easily adapting to the demands made upon them.