A Feasible Web-Conference-Style Remote Simulation using Demonstration Video Clips in Anaesthesia under the COVID-19 Outbreaks: A Preliminary Survey Study

Objective:The Coronavirus disease-2019 (COVID-19) outbreak has deprived simulation-based medical education for health care workers. Attendees are strictly prohibited to converge at a simulation training venue because of the COVID-19 outbreaks. To address this issue, we developed a web-conference-style remote simulation program using demonstration video clips. This report introduced the method and described participants’ satisfaction.Methods:This preliminary survey study evaluated learners’ satisfaction in multiple institutions. The Satisfaction Scale Questionnaire with High-Fidelity Clinical Simulation (SSHF) by a 5-degree scale was used to evaluate participants’ satisfaction. The survey was conducted immediately after completing the simulation sessions.Results:Ten (100%) participants (7 anaesthesia individuals, 2 anaesthesia residents and 1 nurse anaesthetist) from nine institutions responded to the survey. All median values of the satisfaction scores were ≥4.0, whereas the median values of scores for environmental fidelity and psychological insecurity were 3.5 and 3.0, respectively (P=0.005).Conclusion:A web-conference-style remote simulation using demonstration video clips is a feasible method for conducting simulation-based medical education under COVID-19 that showed high satisfaction scores. Further, additional studies are required to explore the internal and external validity and the effectiveness of mastery learning

Production of d-Branched-Chain Amino Acids by Lactic Acid Bacteria Carrying Homologs to Isoleucine 2-Epimerase of Lactobacillus buchneri

Isoleucine 2-epimerase (ILEP) is a novel branched-chain amino acid racemase isolated from Lactobacillus buchneri. In this study, we examined production of free d-branched-chain amino acids such as d-valine, d-leucine, and d-allo-isoleucine, using lactic acid bacteria carrying homologs to ILEP. Twelve selected strains of lactic acid bacteria were grown at optimal growth temperatures and accumulation of d-branched-chain amino acids in the medium was monitored in exponential, early stationary, and stationary phases. To analyze the d-branched-chain amino acids, enantiomers in the medium were initially converted into diastereomers using pre-column derivatization with o-phthaldialdehyde plus N-isobutyryl-l-cysteine. The resultant fluorescent isoindole derivatives were analyzed on an octadecylsilyl stationary phase using ultra-high performance liquid chromatography. The analyses revealed that the seven following lactic acid bacteria carrying homologs showing 53–60% amino acid sequence identity to the L. buchneri ILEP accumulate d-branched-chain amino acids: Lactobacillus fermentum and Weissella paramesenteroides produce d-valine, d-leucine, and d-allo-isoleucine; Lactobacillus reuteri, Leuconostoc mesenteroides subsp. mesenteroides, and Leuconostoc gelidum subsp. gasicomitatum accumulate d-leucine and d-allo-isoleucine; and Lactobacillus vaginalis and Leuconostoc pseudomesenteroides produce d-allo-isoleucine. These results suggest that d-branched-chain amino acids are produced by a variety of lactic acid bacteria species, particularly those carrying homologs to the ILEP

A new thermo-time domain reflectometry approach to quantify soil ice content at temperatures near the freezing point

Soil ice content (θi) is an important property for many studies associated with cold regions. In situ quantification of θi with thermo-time domain reflectometry (TDR) at temperatures near the freezing point has been difficult. The objective of this study is to propose and test a new thermo-TDR approach to determine θi. First, the liquid water content (θl) of a partially frozen soil is determined from a TDR waveform. Next, a pulse of heat is applied through the thermo-TDR sensor to melt the ice in the partially frozen soil. Then, a second TDR waveform is obtained after melting to determine the θl, which is equivalent to the total water content (θt ) of the partially frozen soil. Finally, θi is calculated as the difference between θt and θl. The performance of the new approach was evaluated in sand and loam soils at a variety of θ t values. The new approach estimated θt , θl, and θi accurately. The root mean square errors (RMSE) of estimation were 0.013, 0.020, and 0.023 m3 m−3 for sand, and 0.041, 0.026, and 0.031 m3 m−3 for loam. These RMSE values are smaller than those reported in earlier thermo-TDR studies. Repeating the thermo-TDR measurements at the same location on the same soil sample caused decreased accuracy of estimated values, because of radial water transfer away from the heater tube of the thermo-TDR sensor. Further research is needed to determine if it is possible to obtain accurate repeated measurements. The use of a dielectric mixing model to convert the soil apparent dielectric constant to θl improved the accuracy of this approach. In our investigation, application of a small heat intensity until the partially frozen soil temperature became larger than about 1°C was favorable. The new method was shown to be suitable for estimating ice contents in soil at temperatures between 0°C and -2°C, and it could be combined with the volumetric heat capacity or thermal conductivity thermo-TDR based methods, which measured ice content at colder temperatures. Thus, the thermo-TDR technique could measure θi at all temperatures

Preoperative Butyrylcholinesterase Level as an Independent Predictor of Overall Survival in Clear Cell Renal Cell Carcinoma Patients Treated with Nephrectomy

The prognostic factors for the overall survival (OS) of clear cell renal cell carcinoma (ccRCC) patients treated with nephrectomy are not well defined. In the present study, we investigated the prognostic significance of preoperative butyrylcholinesterase (BChE) levels in 400 ccRCC patients undergoing radical or partial nephrectomy from 1992 to 2013 at our institution. Univariate and multivariate analyses were performed to determine the clinical factors associated with OS. Among the enrolled patients, 302 were diagnosed with organ-confined disease only (T1-2N0M0), 16 with lymph node metastases, and 56 with distant metastases. The median preoperative BChE level was 250 U/L (normal range, 168–470 U/L), and median follow-up period was 36 months. The 3-year OS rate in patients with preoperative BChE levels of ≥100 U/L was significantly higher than in those with levels of <100 U/L (89.3% versus 77.7%, P=0.004). On univariate analysis, performance status; anemia; hypoalbuminemia; preoperative levels of BChE, corrected calcium, and C-reactive protein; and distant metastasis status were significantly associated with OS. Multivariate analysis revealed that preoperative BChE levels and distant metastasis status were significantly associated with OS. Our findings suggest a possible role of preoperative BChE levels as an independent predictor of OS after nephrectomy in ccRCC patients

Development of eosinophilic granulomatosis with polyangiitis during the clinical course of microscopic polyangiitis: A case report

Rationale: Eosinophilic granulomatosis with polyangiitis (EGPA) is belongs to the antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) subgroups. EGPA, unlike other subgroups of AAV, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis, has the unique feature that both ANCA and eosinophilic inflammation are involved in its pathogenesis. Although AAV often relapses, there are currently no reports of EGPA developing during other subgroups of AAV. Herein, we document a case of EGPA that developed during the clinical course of MPA.Patient concerns: A 61-year-old Japanese woman was diagnosed with MPA based on interstitial lung disease and myeloperoxidase-ANCA positivity. After starting immunosuppression therapy, including prednisolone and tacrolimus, she was expected to achieve clinical remission. Nonetheless, she occasionally experienced MPA relapse, which required an increased prednisolone dose, rituximab, intravenous cyclophosphamide, and plasma exchange. Three years after MPA onset, she developed renal amyloidosis; thus, subcutaneous tocilizumab was added to her regimen. Following clinical remission, the administration interval of her subcutaneous tocilizumab therapy was extended and immunosuppressants were discontinued. She then developed bronchial asthma and mild eosinophilia (eosinophilic count: ~1000/μL). Further, a year later, she underwent total hip replacement using a titanium implant. Subsequently, she developed abnormal sensation in both hands, numbness, and muscle weakness, as well as palpable purpura and massive eosinophilia (eosinophilic count: ~8500/μL).Diagnosis: We diagnosed the patient with EGPA based on 5 items (asthma, multiple mononeuropathies, sinus abnormality, and extravascular eosinophils) of the 1990 American College of Rheumatology classification criteria.Interventions: We administered 400 mg/kg intravenous immunoglobulin for 5 consecutive days, 300 mg mepolizumab subcutaneously every 4 weeks, and 40 mg/day prednisolone following pulsed methylprednisolone therapy (1000 mg/day for 3 consecutive days).Outcomes: After these treatments, the patient’s symptoms improved, and eosinophilic count and inflammatory markers declined.Lessons: The present case suggests that EGPA can be induced by the development of eosinophilic inflammation in other subgroups of AAV.Abbreviations: AAV = ANCA-associated vasculitis, ANCA = antineutrophil cytoplasmic autoantibody, CCL = chemokine (C–C motif) ligands, CRP = C-reactive protein, EGPA = eosinophilic granulomatosis with polyangiitis, IL = interleukin, ILC2 = group 2 innate lymphoid cells, ILD = interstitial lung disease, MPA = microscopic polyangiitis, MPO = myeloperoxidase, mPSL = methylprednisolone, PSL = prednisolone, TAC = tacrolimus, TCZ = tocilizumab, Th2 = T helper 2

Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS:A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau

Objective To determine the diagnostic and prognostic significance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma of patients with amyotrophic lateral sclerosis (ALS) and to investigate whether the combined use of those biomarker candidates can improve their diagnostic performance. Methods This was a single-center, prospective, longitudinal study. CSF and plasma samples were collected at the time of enrollment from a discovery cohort of 29 patients with ALS and 29 age-matched controls without neurodegenerative disease. In a validation cohort, there were 46 patients with ALS, and 46 control (not age-matched) patients with motor weakness resulting from neuromuscular diseases. NfL, TDP-43, and t-tau levels in CSF and plasma were measured using ultrasensitive single molecule assay (Simoa) technology. Results The following findings were reproducibly observed among the discovery and validation cohorts: increased levels of CSF NfL, plasma NfL, and CSF TDP-43 in ALS compared with control groups; shorter survival associated with higher levels of CSF and plasma NfL. When the CSF NfL and CSF TDP-43 levels were combined, the areas under the ROC curves (AUC) were slightly improved relative to AUCs for each biomarker alone. Interpretation CSF and plasma NfL may not only serve as diagnostic biomarkers but also provide a measure of disease progression. CSF TDP-43 is also useful as a diagnostic biomarker of ALS, but has no prognostic value. The combined use of CSF NfL and CSF TDP-43 may be a useful biomarker for the diagnosis of ALS

Ring-fused porphyrins: extension of π-conjugation significantly affects the aromaticity and optical properties of the porphyrin π-systems and the Lewis acidity of the central metal ions

Here, we report the effects of ring fusion, which causes expansion of the π-conjugation circuits of the porphyrin derivatives to the fused meso-aryl groups, on the aromaticity and the magnetic properties of porphyrin derivatives. These studies revealed the facts that the ring fusion with five-membered rings causes not only the remarkable red shifts of the absorption bands and narrowed HOMO–LUMO gaps, but also the contribution of anti-aromatic resonance forms to the magnetic properties as observed in the 1H NMR spectra. The optical absorption and magnetic circular dichroism (MCD) spectroscopies indicate that the increase in the number of the fused rings causes stabilization of the LUMO level of the porphyrin derivatives and as a result induces the loosening of the LUMO degeneracy that is generally observed for porphyrins. The electronic structure of a quadruply fused porphyrin derivative was experimentally clarified by the ESR studies on the 1e−-oxidized and 1e−-reduced species in THF. Furthermore, we revealed the substituent effects of the fused meso-aryl groups of quadruply fused porphyrins (QFPs) on the crystal structures, absorption spectra and redox potentials; the sensitiveness of the substituent effects shows that the π-conjugation circuits extended to the fused meso-aryl groups. Additionally, the elongation of the bond lengths between the pyrrolic nitrogen and the central metal ions in QFP–metal complexes causes a remarkable increase of the Lewis acidity of the central metal ions

Site-specific isotope labeling of long RNA for structural and mechanistic studies

A site-specific isotope labeling technique of long RNA molecules was established. This technique is comprised of two simple enzymatic reactions, namely a guanosine transfer reaction of group I self-splicing introns and a ligation with T4 DNA ligase. The trans-acting group I self-splicing intron with its external cofactor, ‘isotopically labeled guanosine 5′-monophosphate’ (5′-GMP), steadily gave a 5′-residue-labeled RNA fragment. This key reaction, in combination with a ligation of 5′-remainder non-labeled sequence, allowed us to prepare a site-specifically labeled RNA molecule in a high yield, and its production was confirmed with 15N NMR spectroscopy. Such a site-specifically labeled RNA molecule can be used to detect a molecular interaction and to probe chemical features of catalytically/structurally important residues with NMR spectroscopy and possibly Raman spectroscopy and mass spectrometry