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Asymmetric and symmetric dimethylarginines are toxic non-coded amino acids. They are formed by post-translational modifications and play multifunctional roles in some human diseases. Their determination in human blood plasma is performed using capillary electrophoresis with contactless conductivity detection. The separations are performed in a capillary covered with covalently bonded PAMAPTAC polymer, which generates anionic electroosmotic flow and the separation takes place in the counter-current regime. The background electrolyte is a 750 mM aqueous solution of acetic acid with pH 2.45. The plasma samples for analysis are treated by the addition of acetonitrile and injected into the capillary in a large volume, reaching 94.5% of the total volume of the capillary, and subsequently subjected to electrophoretic stacking. The attained LODs are 16 nm for ADMA and 22 nM for SDMA. The electrophoretic resolution of both isomers has a value of 5.3. The developed method is sufficiently sensitive for the determination of plasmatic levels of ADMA and SDMA. The determination does not require derivatization and the individual steps in the electrophoretic stacking are fully automated. The determined plasmatic levels for healthy individuals vary in the range 0.36–0.62 µM for ADMA and 0.32–0.70 µM for SDMA.

Background Diabetic foot infections (DFIs) contribute to the global disability burden. Beta-lactams are the most commonly used antibiotics for treating DFIs. However, the use of antibiotics may lead to disruption of the healthy balance of the gut microbiota, causing dysbiosis. Methods Patients with infected diabetic foot ulcers (iDFUs) were treated with two kinds of beta-lactams (amoxicillin/clavulanic acid or ceftazidime) according to microbial sensitivity of causative agents via bolus or continuous administration modes. Changes in the gut microbiome of patients were analyzed. Diabetic patients without iDFUs were used as a control group. 16 S ribosomal RNA gene amplicon sequencing was performed on stool samples collected from participants. Results Alpha diversity and beta diversity of gut microbiota of treated patients did not show significant differences between bolus and continuous modes. However, significant differences were observed between gut microbiota diversity of treated patients and control group. PCoA plots showed individualized responses of the patient’s gut microbiota to antibiotics at different times using both administration forms associated with the pre-treatment state of microbiota composition. Enterococcus , Sellimonas , and Lachnoclostridium were the common bacterial markers differentially abundant in the gut microbiota of antibiotic-treated patients with iDFUs while Roseburia , Dorea , and Monoglobus were mainly abundant in the gut microbiota of patients without iDFUs. Predicted pathways like “Transporters”, “ABC transporters” and “Phosphotranspherase system (PTS)” were upregulated in the gut microbiome of patients treated with bolus regime which may lead to increased intestinal barrier permeability. Conclusion The present study reported alterations in gut microbiota composition and functionality and provided the bacterial markers as well as potential metabolic signatures associated with each administration mode in patients with iDFUs, which may be used as a reference set for future studies of the effect of antibiotics administration on the gut microbiome of patients with iDFUs. This study shed light on the importance of understanding the effect of antibiotic administration form on gut microbiome in patients with iDFUs. Trial registration The DFIATIM Clinical Trial (Full title: “Rationalisation of ATB therapy in diabetic foot infection and its impact on the intestinal microbiota”) is submitted to the European Union Clinical Trials Database under the EudraCT Number: 2019-001997-27. The date of registration is July 17th, 2020.

Aim of the study was to compare metabolic response of leg skeletal muscle during functional electrical stimulation-driven unloaded cycling (FES) to that seen during volitional supine cycling. Fourteen healthy volunteers were exposed in random order to supine cycling, either volitional (10-25-50 W, 10 min) or FES assisted (unloaded, 10 min) in a crossover design. Whole body and leg muscle metabolism were assessed by indirect calorimetry with concomitant repeated measurements of femoral venous-arterial differences of blood gases, glucose, lactate and amino acids. Unloaded FES cycling, but not volitional exercise, led to a significant increase in across-leg lactate production (from -1.1±2.1 to 5.5±7.4 mmol/min, p<0.001) and mild elevation of arterial lactate (from 1.8±0.7 to 2.5±0.8 mM). This occurred without widening of across-leg veno-arterial (VA) O2 and CO2 gaps. Femoral SvO2 difference was directly proportional to VA difference of lactate (R2 = 0.60, p = 0.002). Across-leg glucose uptake did not change with either type of exercise. Systemic oxygen consumption increased with FES cycling to similarly to 25W volitional exercise (138±29% resp. 124±23% of baseline). There was a net uptake of branched-chain amino acids and net release of Alanine from skeletal muscle, which were unaltered by either type of exercise. Unloaded FES cycling, but not volitional exercise causes significant lactate production without hypoxia in skeletal muscle. This phenomenon can be significant in vulnerable patients' groups.

Methyltriphenylphosphonium (TPMP) salts have been widely used to measure the mitochondrial membrane potential and the triphenylphosphonium (TPP+) moiety has been attached to many bioactive compounds including antioxidants to target them into mitochondria thanks to their high affinity to accumulate in the mitochondrial matrix. The adverse effects of these compounds on cellular metabolism have been insufficiently studied and are still poorly understood. Micromolar concentrations of TPMP cause a progressive inhibition of cellular respiration in adherent cells without a marked effect on mitochondrial coupling. In permeabilized cells the inhibition was limited to NADH-linked respiration. We found a mixed inhibition of the Krebs cycle enzyme 2-oxoglutarate dehydrogenase complex (OGDHC) with an estimated IC50 3.93 [3.70-4.17] mM, which is pharmacologically plausible since it corresponds to micromolar extracellular concentrations. Increasing the lipophilic character of the used TPP+ compound further potentiates the inhibition of OGDHC activity. This effect of TPMP on the Krebs cycle ought to be taken into account when interpreting observations on cells and mitochondria in the presence of TPP+ derivatives. Compounds based on or similar to TPP+ derivatives may also be used to alter OGDHC activity for experimental or therapeutic purposes.

BackgroundCOVID-19, an infectious disease caused by SARS-CoV-2, was shown to be associated with an increased risk of new-onset diabetes. Mechanisms contributing to the development of hyperglycemia are still unclear. We aimed to study whether hyperglycemia is related to insulin resistance and/or beta cell dysfunction.Materials and methodsSurvivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: corticosteroids use, indirect calorimetry, and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI). Resting energy expenditure (REE) and respiratory quotient (RQ) was calculated from the gas exchange and nitrogen losses.Results26 patients (out of 37) with complete outcome data were included in the analysis (age ~59.0 years; BMI ~ 30.4, 35% women). Patients were hypermetabolic at T0 (30.3 ± 4.0 kcal/kg lean mass/day, ~120% predicted) but REE declined over 6 months (ΔT6-T0 mean dif. T6-T0 (95% CI): −5.4 (−6.8, −4.1) kcal/kg FFM/day, p < 0.0001). 17 patients at T0 and 13 patients at T6 had hyperglycemia. None of the patients had positive islet autoantibodies. Insulin sensitivity in T0 was similarly low in hyperglycemic (H) and normoglycemic patients (N) (T0 ISIH = 3.12 ± 1.23, ISIN = 3.47 ± 1.78, p = 0.44), whereas insulin response was lower in the H group (DIH = 3.05 ± 1.79 vs DIN = 8.40 ± 5.42, p = 0.003). Over 6 months ISI (ΔT6-T0 mean dif. T6-T0 for ISI (95% CI): 1.84 (0.45, 3.24), p = 0.01)) increased in the H group only.ConclusionsPatients with severe COVID-19 had increased REE and insulin resistance during the acute phase due to the infection and corticosteroid use, but these effects do not persist during the follow-up period. Only patients with insufficient insulin response developed hyperglycemia, indicating that beta cell dysfunction, rather than insulin resistance, was responsible for its occurrence.

The completed environmental study was concerned with assessing the exposure of the Czech population to polybrominated diphenyl ethers (PBDEs). Simultaneously, the levels of polychlorinated pollutants such as polychlorinated biphenyls (PCBs) and chlorinated diphenyl ethanes (DDTs) were also monitored. The pollutant levels were newly measured in solid fat tissue removed during plastic surgery. A total of 107 samples of fat were taken from 19–76-year-old volunteers. A total of 16 PBDE congeners were determined, of which only six occur in more than 38% of fat tissue samples. The total PBDE level attains an average value of 3.31 ng/g, which is 25% less than was measured in 2009. On the other hand, there was an increase in the levels of two PCB congeners, which was caused by an increase of the total PCB concentration from level of 625.5 ng/g, published in 2009, to the current level of 776 ng/g. The level of DDTs decreased and currently has a value of 467.4 ng/g, which is about 24% lower than in 2009. The contamination of obese middle-aged women in Czechia by more modern types of pollutants, such as PBDEs, is incomparably lower than that by PCBs and DDTs and is also decreasing in time.

Polyunsaturated fatty acids of the n-3 series (n-3 PUFA) exhibit a number of favorable effects on the human organism and it is desirable to increase their intake in the diet. For this purpose, flaxseed oil was added to a chicken-feed mixture for the production of meat and eggs. The content of n-3 PUFA in the obtained meat was increased from 250 mg (reference value) to 900 mg in 100 g of meat and from 110 mg (reference value) to 190 mg in 100 g of whole egg; the enriched products are designated as omega-3 meat and omega-3 eggs. Omega-3 meat and eggs were subsequently fed for a period of eight weeks in an amount of 480 g of meat and four eggs (228 g netto) a week to a group of 14 healthy volunteers, whose body composition parameters were measured and blood was analyzed biochemically to determine blood lipids, coagulation parameters, plasma, and erythrocyte fatty acid spectrum composition. A control group of 14 volunteers was fed normal chicken and eggs in the same regime. The performed dietary intervention increases the intake of long-chain PUFA (LC-PUFA) by 37 mg per day, which represents 7–15% of the recommended daily dose. The performed tests demonstrated that the consumption of omega-3 enriched meat and eggs significantly increases the content of n-3 PUFA in the erythrocytes, which are a long-term indicator of fatty acid intake. This intervention has no demonstrable effect on the basic body parameters, such as body weight, fat content, Body Mass Index (BMI), and also on the plasma cholesterol level, high-density lipoprotein (HDL), low-density lipoprotein (LDL), blood clotting and inflammation markers, and omega-3 index.

Background/Aims: Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Methods: Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Results: Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p < 0.0001) and GIP response (p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly (p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. Conclusions: An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent.

Unit testing is an attractive quality management tool in the software development process, however, practical obstacles make it difficult to use unit tests for performance testing. We present Stochastic Performance Logic, a formalism for expressing performance requirements, together with interpretations that facilitate performance evaluation in the unit test context. The formalism and the interpretations are implemented in a performance testing framework and evaluated in multiple experiments, demonstrating the ability to identify performance differences in realistic unit test scenarios.

The COVID-19 pandemic presents several challenges for managing patients with acute coronary syndrome (ACS). Modified treatment algorithms have been proposed for the pandemic. We assessed new algorithms proposed by The European Association of Percutaneous Cardiovascular Interventions (EAPCI) and the Acute Cardiovascular Care Association (ACCA) on patients with ACS admitted to the hospital during the COVID-19 pandemic. The COVID-19 period group (CPG) consisted of patients admitted into a high-volume centre in Prague between 1 February 2020 and 30 May 2020 (n = 181). The reference group (RG) included patients who had been admitted between 1 October 2018 and 31 January 2020 (n = 834). The proportions of patients with different types of ACS admitted before and during the pandemic did not differ significantly: in all ACS patients, KILLIP III-IV class was present in 13.9% in RG and in 9.4% of patients in CPG (p = 0.082). In NSTE-ACS patients, the ejection fraction was lower in the CPG than in the RG (44.7% vs. 50.7%, respectively; p < 0.001). The time from symptom onset to first medical contact did not differ between CPG and RG patients in the respective NSTE-ACS and STEMI groups. The time to early invasive treatment in NSTE-ACS patients and the time to reperfusion in STEMI patients were not significantly different between the RG and the CPG. In-hospital mortality did not differ between the groups in NSTE-ACS patients (odds ratio in the CPG 0.853, 95% confidence interval (CI) 0.247 to 2.951; p = 0.960) nor in STEMI patients (odds ratio in CPG 1.248, 95% CI 0.566 to 2.749; p = 0.735). Modified treatment strategies for ACS during the COVID-19 pandemic did not cause treatment delays. Hospital mortality did not differ.