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Low plasma concentrations are expected during prolonged RRT because of persistent extracorporeal removal, absent renal reabsorption and enhanced metabolic loss due to circuit-induced oxidative stress. A dosage of twice 1 g vitamin C daily may be necessary to achieve normal plasma concentrations during RRT, but more studies are needed. There is no available evidence that high doses of vitamin C administered over a short period can induce oxalate stones or has pro-oxidant effects. CONCLUSIONS Supplementing vitamin C 1 g twice daily to critically ill patients has a solid pathophysiological rationale and a good safety profile. Patients on RRT probably need similar doses as critically ill patients not receiving RRT. Intravenous vitamin C in a dose of 2 g/day may be necessary to achieve normal plasma concentrations during RRT. However, data on dose adjustment of vitamin C during intermittent or chronic RRT are sparse and require more thorough pharmacokinetic and dose-response studies.The objective of the study is to evaluate the sensitivity of the new criteria for the classification of systemic lupus erythematosus (SLE), when applied to real SLE cases. We retrospectively reviewed the electronic medical records of 100 consecutive patients who visited St. Luke's International Hospital. Patients were included if they were clinically diagnosed as having SLE and excluded if they had other autoimmune disease or if they were less than 18 years old. Each patient was evaluated if they satisfied the American College of Rheumatology (ACR) 1997 classification criteria (1997 criteria), 2012 Systemic Lupus International Collaborating Clinics criteria (2012 criteria), or 2019 ACR/European League Against Rheumatism (EULAR) criteria. Among the 100 patients, the sensitivity of the 1997, 2012, and 2019 criteria was, 97, 99, and 92%, respectively. The total patient score with the 2019 criteria ranged from 12 to 44 (mean, 27.3). All patients who were classified as non-SLE with the 2019 criteria had an anti-nuclear antibody (ANA) titre of less then 180. The 2019 criteria for SLE accomplished modestly high sensitivity in the real-world practice, but not as high as the 1997 and 2012 criteria. They possibly misclassify the real SLE cases as non-SLE, especially if patients have a low titre ( less then 180) of ANA.AIM To assess the phospholipid bilayer of white blood cells (WBCs) and the ability of leukocytes to generate reactive oxygen species (ROS) in rats orally exposed to GdVO4Eu3+ nanoparticle (VNP) solution for 2 weeks by fluorescent probes-ortho-hydroxy derivatives of 2,5-diaryl‑1,3‑oxazole. METHODS Steady-state fluorescence spectroscopy, i.e., a study by the environment-sensitive fluorescent probes 2‑(2'-OH-phenyl)-5-(4'-phenyl-phenyl)-1,3-oxazole (probe O6O) and 2‑(2'-OH-phenyl)-phenanthro[9,10]-1,3-oxazole (probe PH7), and flow cytometry, i.e., analysis of 2',7'-dichlorofluorescein (DCF), a product of a dye 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), fluorescence in CD45+/7-aminoactinomycin D (7-AAD)- cells, were used to evaluate the state of cell membranes and reactive oxygen species (ROS) generation in leukocytes of rats orally exposed to gadolinium orthovanadate nanoparticles(VNPs). RESULTS No significant changes were detected in the spectra of the fluorescent probes bound to the WBCs from the rats orally exposed to nanoparticles in comparison with the corresponding spectra of the probes bound to the cells from the control group of animals. This indicates that in the case of the rats orally exposed to nanoparticles, no noticeable changes in physicochemical properties (i.e., in the polarity and the proton-donor ability) are observed in the lipid membranes of WBCs in the region where the probes locate. There was no statistically significant difference in the amount of ROShigh viable leukocytes in rats treated with VNPs and control samples. CONCLUSION Neither changes in the physical and chemical properties of the leukocyte membranes nor in ROS generation by WBCs are detected in the rats orally exposed to VNP solution for 2 weeks.Excitatory neurotransmission relies on the precise targeting of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors to the neuronal plasma membrane. Activity-dependent ubiquitination of AMPA receptor (AMPAR) subunits sorts internalised receptors to late endosomes for degradation, which ultimately determines the number of AMPARs on neuronal membrane. Our recent study has demonstrated a functional cross-talk between the phosphorylation and ubiquitination of the GluA1 subunit in mammalian central neurons. However, the existence of such a cross modulation for the GluA2 subunit remains unknown. Here, we have shown that bicuculline induced GluA2 ubiquitination on the same lysine residues (Lys-870 and Lys-882) in the C-terminal as those elicited by the AMPA treatment. Interestingly, bicuculline-induced ubiquitination was markedly enhanced by the phospho-mimetic GluA2 S880E mutant. Pharmacological activation of protein kinase C (PKC) by phorbol ester, which mediates the phosphorylation of GluA2 at Ser-880, augmented bicuculline-induced ubiquitination of GluA2 in cultured neurons. This effect was specific for the GluA2 subunit because phorbol ester did not alter the level of GluA1 ubiquitination. However, phorbol ester-induced enhancement of GluA2 ubiquitination did not require Ser-880 phosphorylation. C646 price This suggests that pseudo-phosphorylation of Ser-880 is sufficient but is not necessary for the augmentation of bicuculline-induced GluA2 ubiquitination. Collectively, these data provide the first demonstration of subunit-specific modulation of AMPAR ubiquitination by the PKC-dependent signalling pathway in mammalian central neurons.Right atrial (RA) and right ventricular (RV) parameters assessed by traditional echocardiography lack sensitivity to identify pulmonary embolism (PE). We sought to determine if alterations in RV free wall longitudinal strain (FWS) would be present in PE patients and improve evaluation. This retrospective study comprised of 84 consecutive PE patients from 2 centres, with adequate transthoracic echocardiography (TTE) images for RV FWS analysis. PE patients were compared to 66 healthy controls. Compared to controls, PE patients had increased RV parasternal long-axis diameter (RVPLAX) (33.4 ± 5.8 mm vs 39.9 ± 4.1 mm) and RA area (17.4 ± 5.6 cm2 vs 14.5 ± 3.1 cm2) (p less then 0.001 for both). RV function was reduced in PE patients (RV fractional area change 31.1 ± 13.2% vs 41.7 ± 9.1%, TAPSE 17.0 ± 4.5 vs 21.3 ± 2.2 mm; p less then 0.001 for both). RV FWS was reduced in PE patients (-14.4 ± 7.2% vs - 26.0 ± 4.4%, p less then 0.001). RV FWS was the best discriminator for PE (AUC 0.912). In comparative multiple logistic regression models for PE, the model which included traditional measures of RV size and function and RV FWS, produced a powerful classifier (AUC 0.
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