Search

Since the beginning of 2020, tetracycline (TC), such as minocycline (MINO), has been used to inhibit coronavirus disease 2019 (COVID-19). Traditional Japanese Kampo medicine, such as Saiko-keishi-to (SKT), has recently received a lot of attention for its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects. We describe a COVID-19 patient treated with MINO and SKT in anticipation of their anti-SARS-CoV-2 properties. A 90-year-old male patient with Alzheimer’s disease was referred to a medical clinic due to fever, appetite loss, and general malaise. Based on positive SARS-CoV-2 rapid antigen tests, he was diagnosed with COVID-19. He did not have COVID-19 pneumonia, but he had difficulty in eating on his own. As a result, he was referred to a hospital for admission. After admission, he was treated with molnupiravir to avoid aggravation. Seven days after his admission, he was discharged. After his discharge, he was referred to our hospital as an outpatient due to a prolonged mild fever and general malaise. As a precaution, a real-time reverse transcription-polymerase chain reaction (RT-PCR) test was performed, which yielded a positive result. Therefore, the aforementioned symptoms were thought to be caused by prolonged COVID-19. He was treated with MINO and SKT due to the anti-viral properties of these two drugs. The RT-PCR test became negative 7 days after receiving this treatment, and the fever and general malaise subsided.

Membranous nephropathy (MN) is a disease characterized by deposition of immune complexes on the glomerular basement membrane. More than 10 specific antigens for MN including M-type phospholipase A2 receptor (PLA2R), thrombospondin type-1 domain-containing 7A (THSD7A), exostosin 1/exostosin 2 (EXT1/EXT2) and neural epidermal growth factor-like 1 (NELL1) have so far been identified. Since the clinicopathologic characteristics of each type of MN in Japanese are not well understood, we first examined 107 cases of MN by immunohistochemistry for four antigens (PLA2R, THSD7A, EXT1, and NELL1) (MN-cohort). Of those 107 cases, 40% were PLA2R-positive, 13% were NELL1-positive, 11% were THSD7A-positive, 5% were EXT1-positive, 2% were PLA2R and NELL1-double-positive, and 29% were quadruple-negative. In one case of PLA2R and NELL1-double-positive, the first biopsy showed PLA2R-positive and the second biopsy showed PLA2R and NELL1-double-positive. Of the 16 cases of NELL1-positive, 12.5% had colon cancer, 18.8% had rheumatic diseases treated with bucillamine, and 63% had type 2 diabetes mellitus (T2DM). Next, 34 patients diagnosed with MN who had rheumatoid arthritis (RA) were examined (RA-MN cohort). Of those 34 patients, 79% were NELL1-positive, 6% were PLA2R-positive, and 15% were quadruple-negative. In the RA-MN cohort, 56% had a history of bucillamine use. In conclusion, NELL1-associated MN is a common MN in patients with RA using bucillamine and may also be associated with T2DM.

N/A

In this article, vertical electric fields (including skywaves) produced by lightning return strokes at distances ranging from 100 to 958 km have been computed using the finite-difference time-domain (FDTD) method in the 2-D spherical coordinate system. The return stroke is represented by the original transmission-line (TL) model (with no current decay with height and abrupt current termination at the channel top), the modified TL model with linear current decay with height (MTLL model), the modified TL model with exponential current decay with height (MTLE model), or the Hertzian dipole (HD) model. All the TL-type models include propagation delay, while in the HD model the current changes with time, but does so simultaneously in all channel sections; that is, without any propagation delay. The HD model predicts considerably higher fields than the TL-type models, if the same channel length is employed. The HD model with an unrealistically small channel length of 0.7 km yields electric field peaks similar to those produced by TL-type models with a 7-km channel. Ground waves and skywaves computed using the HD model have faster rise and decay times (shorter pulsewidths) than those computed using a TL-type model. Electric fields produced by a longer risetime current are less attenuated due to propagation over lossy ground when a TL-type model is used, while they are more attenuated if the HD model is employed. The opposite trends are related to the fact that the radiation field peak is proportional to the product of the current and propagation speed for a TL-type model, while for the HD model, it is proportional to the product of the time derivative of current and channel length. In the TL model, abrupt termination of significant current at the channel top results in the so-called mirror image (abrupt radiation field polarity change). This artifact does not occur in the framework of the MTLL model and is negligible in the MTLE model with λ = 2 km and H = 7 km.

To investigate the longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) thickness after epiretinal membrane (ERM) vitrectomy with internal limiting membrane (ILM) peeling, examine associations between pRNFL thickness and central retinal sensitivity, and identify predictors of postoperative pRNFL thickness.Prospective, observational, cohort study.This study enrolled 82 eyes of 82 Japanese patients that underwent surgery for unilateral idiopathic ERM, with their fellow eyes as controls. pRNFL thickness was measured in 4 (superior, temporal, inferior, and nasal) quadrants preoperatively and at 1, 3, 6, and 12 months postoperatively. Microperimetry was performed at 12 months postoperatively to evaluate central retinal sensitivity. Regression tree analysis was performed to predict pRNFL thickness at 12 months postoperatively.The temporal quadrant showed continuous pRNFL thinning after surgery, reaching statistical significance at 3, 6, and 12 months postoperatively (all P 0.001). The pRNFL thicknesses in the fellow eyes significantly increased at all postoperative time points (all P 0.001). At 12 months postoperatively, the average central retinal sensitivity was significantly correlated with the temporal pRNFL thickness in the eyes with ERM (r = 0.372, P 0.001); no significant correlation was found in the fellow eyes. Regression tree analysis showed that the preoperative pRNFL thickness in the temporal quadrant and patient age were the main determinants of the temporal pRNFL thickness at 12 months postoperatively.The risk of deterioration of central retinal sensitivity after ERM vitrectomy with internal limiting membrane peeling should be considered for patients with thin temporal pRNFLs and older adults.

N/A

Study Design: Prospective cohort study.Purpose: This study aims to examine changes in spinopelvic alignment, sagittal global balance, and low back pain (LBP) following the removal of knee flexion contracture by total knee arthroplasty (TKA).Overview of Literature: The limitation of the knee extension was correlated with the decrease in lumbar lordosis (LL). Currently, there are no studies evaluating the spinopelvic alignment and LBP before and after TKAs.Methods: Sagittal spinopelvic alignment was evaluated in 110 subjects using radiographs of the whole spine. Parameters measured in this study included sagittal vertical axis (SVA), LL, sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). The distribution of sagittal plane modifier grade was evaluated according to the Scoliosis Research Society-Schwab classification of adult spinal deformity (ASD). Consequently, personal history related to LBP was obtained, and the association of pre- and postoperative LBP and spinopelvic alignment was investigated.Results: Preoperatively, 66% of all subjects showed LBP and mostly exhibited anteriorly shifted global imbalance associated with a decrease in LL and knee flexion contractures, and the subject who had severe flexion contracture of the knee joint showed more forwardly shifted global balance with backward PT and decrease in LL. After TKAs, the knee flexion contractures were eliminated in most cases, and one-third of subjects experienced decrease in LBP. However, SVA increased more and associated with slight decrease of PT and increase of SS. No significant differences were confirmed between pre- and postoperative values of LL and PI. In addition, there were no significant differences in postoperative values of spinopelvic parameters between subjects with and without relieved LBP.Conclusions: Although one-third of subjects experienced decrease of LBP after TKAs, the sagittal global imbalance was not restored through the removal of knee flexion contracture.

In the boiler feed-water system of thermal power plants, iron oxide scale is generated due to the corrosion of piping, which decreases the effectiveness of the heat exchanger in the boiler and contributes to reduced power generation efficiency. Scale removal can prevent this phenomenon, which consequently results in decreased carbon dioxide emission. In a previous study, an iron scale removal system was developed using superconducting magnets, and high-gradient magnetic separation (HGMS) experiments were conducted using the height difference between the inflow and outflow tanks. As a result, particles were intensively captured by the filters at the inflow side. We succeeded in eliminating this capture by properly controlling the applied magnetic field. However, because the suspension also flowed due to the height difference in this experiment, the problems of partial blockage of the filter and the resulting decrease in the flow rate were not resolved even under the controlled magnetic field. In this study, HGMS experiments were conducted under a constant flow rate with a large pump in a large-scale system having a filter diameter of 300 mm to simulate a boiler feed-water system or chemical cleaning line. Furthermore, we investigated the feasibility of the large-scale HGMS system and elucidated the scale-up effect on the amount captured and the spatial distribution of the captured particles on the filters. Based on these results, a plant-scale HGMS system (800 mm filter diameter) was designed.

Partial bacterial genome reduction by genome engineering can improve the productivity of various metabolites, possibly via deletion of non-essential genome regions involved in undesirable metabolic pathways competing with pathways for the desired end products. However, such reduction may cause growth defects. Genome reduction of Bacillus subtilis MGB874 increases the productivity of cellulases and proteases but reduces their growth rate. Here, we show that this growth defect could be restored by silencing redundant or less important genes affecting exponential growth by manipulating the global transcription factor AbrB. Comparative transcriptome analysis revealed that AbrB-regulated genes were upregulated and those involved in central metabolic pathway and synthetic pathways of amino acids and purine/pyrimidine nucleotides were downregulated in MGB874 compared with the wild-type strain, which we speculated were the cause of the growth defects. By constitutively expressing high levels of AbrB, AbrB regulon genes were repressed, while glycolytic flux increased, thereby restoring the growth rate to wild-type levels. This manipulation also enhanced the productivity of metabolites including γ-polyglutamic acid. This study provides the first evidence that undesired features induced by genome reduction can be relieved, at least partly, by manipulating a global transcription regulation system. A similar strategy could be applied to other genome engineering-based challenges aiming toward efficient material production in bacteria.

Conformational fluctuation, namely, protein interconversion between different conformations, is crucial to protein function. Outer surface protein A (OspA), comprising N- and C-terminal globular domains linked by a central β-sheet, is expressed on the surface of

We have been developing a scale removal system utilizing a superconducting magnet that can remove the iron oxide scale from the boiler feed-water in the thermal power plants. Scale removal can prevent a decrease in the power generation efficiency and contribute to reduce the carbon dioxide emissions. In our previous study, we conducted the large-scale experiments for practical use, but model particles were intensively captured by the inflow side filter. In this paper, we succeeded to homogenize the distribution of captured particles in the filter stacks by controlling the applied magnetic field strength. In addition, magnetic field strength dependency of filter blockage was examined in the lab-scale experiments to clarify a detailed mechanism of blockage.

Pancreatic cancer is an extremely treatment-resistant neoplasm to chemotherapy and immunotherapy. The combination of photon beam irradiation and anti-CTLA-4 antibody (C4) for the anti-tumor effect enhancement at local and distant tumors (abscopal tumors) was investigated using the pancreatic ductal adenocarcinoma (PDAC) mouse model. Pan02 cells were bilaterally inoculated to both legs of C57BL/6 mice. High dose photon beams in a hypofractionation or a single fraction were delivered to the tumors on one leg. Monotherapy with C4 via i.p. was not effective for PDAC. The high dose irradiation to the local tumors produced significant shrinkage of irradiated tumors but did not induce the abscopal responses. In contrast, the combination therapy of high dose photon beam irradiation in both hypofractionation and a single fraction with C4 enhanced the anti-tumor effect for abscopal tumors with significantly prolonged overall survival. The flow cytometric analysis revealed that the combination therapy dramatically decreased the regulatory T cell (Treg) proportion while increasing the cytotoxic T lymphocytes in both local and abscopal tumors. These results suggest that high dose photon beam irradiation plays an important role in C4 therapy to enhance the abscopal response with immune microenvironment changes in PDAC, regardless of the fractionation in radiation therapy.

Objective To investigate the refractive change and optical biometry dynamics after 25-gauge vitrectomy without gas tamponade for macular pathology in pseudophakic eyes. Design A prospective observational case series. Participants Patients with pseudophakic eyes who were scheduled for vitrectomy owing to macular pathology by an experienced surgeon (T.S.) at the Hayashi Eye Hospital between March 2019 and February 2020. Methods The primary endpoint was the change in manifest refraction spherical equivalent (MRSE) between baseline (preoperatively) and 3 months postoperatively. The secondary endpoint was the change in optical biometry parameters obtained by swept-source optical coherence tomography–based biometers between baseline and 3 months postoperatively. Optical biometry parameters included corneal curvature and axial length, evaluated by the IOLMaster 700, and intraocular lens position—that is, lens decentration, lens tilt, and aqueous depth (AQD)—evaluated by the CASIA2. Results Thirty-four eyes of 34 patients were enrolled. The mean MRSE values at baseline and 3 months postoperatively were −0.70 ± 1.21 diopter (D) and −0.82 ± 1.27 D, respectively, showing a significant myopic shift of −0.12 ± 0.41 D postoperatively (p = 0.043). There was no significant difference between the pre- and postoperative values of the optical biometry parameters, except for the AQD (4.28 ± 0.34 mm vs 4.27 ± 0.34 mm; p = 0.019). Conclusions The results suggest that replacing the vitreous by the aqueous during vitrectomy induces an average myopic shift of −0.12 D.

In this work, we disclose an advanced general process for the synthesis of tailor-made α-amino acids (α-AAs) via tandem alkylation–second-order asymmetric transformation. The first step is the alkylation of the chiral Ni(II) complex of glycine Schiff base, which is conducted under mild phase-transfer conditions allowing the structural construction of target α-AAs. The second step is based on the methodologically rare second-order asymmetric transformation, resulting in nearly complete precipitation of the corresponding (SC,RN,RC)-configured diastereomer, which can be collected by a simple filtration. The operational convenience and potential scalability of all experimental procedures, coupled with excellent stereochemical outcome, render this method of high synthetic value for the preparation of various tailor-made α-AAs.

In this study, six-membered N-acyliminium ions were generated by the “indirect cation pool” method and reacted with several nucleophiles. These reactions afforded disubstituted piperidine derivatives with high diastereoselectivities and good to excellent yields. The conformations of the obtained N-acyliminium ions were studied by low temperature NMR analyses and DFT calculations and were found to be consistent with the Steven’s hypothesis.

The marine bacterium Rhodovulum sulfidophilum is a nonsulfur phototrophic bacterium, which is known to produce extracellular nucleic acids in soluble form in culture medium. In the present paper, constructing the response regulator ctrA-deficient mutant of R. sulfidophilum, we found that this mutation causes a significant decrease in the extracellular DNA production. However, by the introduction of a plasmid containing the wild type ctrA gene into the mutant, the amount of extracellular DNA produced was recovered. This is the first and clear evidence that the extracellular DNA production is actively controlled by the CtrA in R. sulfidophilum.

This research demonstrates that the methylation of N-benzyl cysteine Schiff bases derived Ni(II) complexes leads to the formation of the corresponding dehydroalanine containing products and cannot be used for preparation of the target -(methyl)cysteine. In sharp contrast, the alternative strategy involving the thiomethylation of the Ni(II) complexes of alanine Schiff bases, is viable and practically attractive approach affording the desired -(methyl)cysteine containing derivatives. This work also reveals a significant, and rather unexpected, difference in the stereochemical performance of proline and 3,5-dihydro-4H-dinaphth[2,1-c:1',2'-e]azepine derived chiral ligands, showing a clear superiority of the former in terms of chemical yields and diastereoselectivity of the -(methyl)cysteine products formation.

Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH.

The diacetylene-group connected chromatic system of [octaethylporphyrin]-[spacer]-[Lewis base] triads (OEP-SPC-LB) was conclusively studied, in which a trigger-like interaction of the terminal LB with trifluoroacetic acid (TFA) dramatically affects the inherent electronic properties of OEP. The 1H NMR, IR, and electronic absorption spectral properties of these OEP derivatives were examined, and were contemplated in view of a cooperative effect of SPC and LB on their OEP nucleus. Based on the results from this study, the structural elements for molecular design will be proposed in order to improve their reversible spectral changes between neutral and acidic media in terms of sensitivity, stability, and visibility to TFA.

Catalytic discrimination between inequivalent formyl groups was achieved using an aniline-Type acid-base catalyst for the regio-, diastereo-, and enantioselective intramolecular cross-Aldol reactions of enolizable dials. Although l-proline gave a mixture of the regio-and stereoisomeric products in the presence of an N-containing 1, 6-dial, the aniline-Type catalyst afforded anti-3, 4-disubstituted pyrrolidine in high regio-, and stereoselectivity beyond the background reaction, which led to the regioisomeric 2, 3-disubstituted products. The mild reactivity of the aniline-Type amine facilitated catalytic discrimination between the inequivalent formyl groups. Kinetic isotope effect studies and reductive amination experiments suggested that the regioselectivity was controlled under the enamine-forming steps.

Gene transfer agents (GTAs) are shaped like bacteriophage particles but have many properties that distinguish them from bacteriophages. GTAs play a role in horizontal gene transfer in nature and thus affect the evolution of prokaryotic genomes. In the course of studies on the extracellular production of designed RNAs using the marine bacterium Rhodovulum sulfidophilum, we found that this bacterium produces a GTA-like particle. The particle contains DNA fragments of 4.5kb, which consist of randomly fragmented genomic DNA from the bacterium. This 4.5-kb DNA production was prevented while quorum sensing was inhibited. Direct observation of the particle by transmission electron microscopy revealed that the particle resembles a tailed phage and has a head diameter of about 40nm and a tail length of about 60nm. We also identified the structural genes for the GTA in the genome. Translated amino acid sequences and gene positions are closely related to those of the genes that encode the Rhodobacter capsulatus GTA. This is the first report of a GTA-like particle from the genus Rhodovulum. However, gene transfer activity of this particle has not yet been confirmed. The differences between this particle and other GTAs are discussed.

The marine bacterium Rhodovulum sulfidophilum is a nonsulfur phototrophic bacterium, which is known to produce extracellular nucleic acids in soluble form in culture medium. In the present paper, constructing the response regulator ctrA-deficient mutant of R. sulfidophilum, we found that this mutation causes a significant decrease in the extracellular DNA production. However, by the introduction of a plasmid containing the wild type ctrA gene into the mutant, the amount of extracellular DNA produced was recovered. This is the first and clear evidence that the extracellular DNA production is actively controlled by the CtrA in R. sulfidophilum.

This paper proposes a flickerless screen-camera communication method using interframe difference to reduce the bit error rate (BER) when the distance between the screen and the smartphone camera becomes long in screen-camera communications. The proposed method uses interframe difference to decode embedded information without interfering with the user's view. Through performance evaluation using an actual screen and a smartphone camera, we show that the proposed method reduces the BER when the communication distance becomes long.

In this study, six-membered N-acyliminium ions were generated by the “indirect cation pool” method and reacted with several nucleophiles. These reactions afforded disubstituted piperidine derivatives with high diastereoselectivities and good to excellent yields. The conformations of the obtained N-acyliminium ions were studied by low temperature NMR analyses and DFT calculations and were found to be consistent with the Steven’s hypothesis.