Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity.

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.

A feasibility study comparing gel immersion endoscopic resection and underwater endoscopic mucosal resection for superficial nonampullary duodenal epithelial tumors.

BACKGROUND: Although gel immersion endoscopic resection (GIER) is a potential alternative to underwater endoscopic mucosal resection (UEMR) for superficial nonampullary duodenal epithelial tumors (SNADETs), comparisons between the two are currently insufficient. METHODS: 40 consecutive procedures performed in 35 patients were retrospectively reviewed; the primary outcome was procedure time, and the secondary outcomes were en bloc and R0 resection rates, tumor and specimen size, and adverse events. RESULTS: Lesions were divided into GIER (n = 22) and UEMR groups (n = 18). The median (range) procedure time was significantly shorter in the GIER group than in the UEMR group (2.75 [1-3.5] minutes vs. 3 2 3 4 5 6 7 8 9 10 minutes; P = 0.01). The en bloc resection rate was 100 % in the GIER group, but only 83.3 % in the UEMR group. The R0 resection rate was significantly higher in the GIER group than in the UEMR group (95.5 % vs. 66.7 %; P = 0.03). The median specimen size was larger in the GIER group than in the UEMR group (14 mm vs. 7.5 mm; P < 0.001). The tumor size was not significantly different between the groups and no adverse events were observed. CONCLUSIONS: GIER is efficacious and safe to treat SNADETs, although additional studies are needed.

[Primary mediastinal large B-cell lymphoma, spindle cell variant demonstrating atypical image findings].

The patient was a 40-year-old woman referred to our hospital after an anterior mediastinal tumor was detected. Imaging findings revealed a tumor with irregular margins and a marked tendency to infiltrate, with some calcification. Rather than malignant lymphoma, thymic carcinoma or high-grade invasive thymoma was suspected. Endobronchial ultrasound-guided transbronchial needle aspiration biopsy and computed tomography-guided needle biopsy were performed, but no diagnosis was made. Mediastinal tumor biopsy by video-assisted thoracic surgery led to the diagnosis of primary mediastinal large B-cell lymphoma, spindle cell variant. A retrospective examination of the needle biopsy specimens revealed that some tissues considered to have been crushed were composed of spindle-shaped lymphoma cells. This study indicates that it is crucial to note that there is a subtype of primary mediastinal large B-cell lymphoma with an unusual pathological morphology.

Effectiveness of a rehabilitation professional's advice and suggestions on a care manager's self-assessment scores of their care management.

[Purpose] To verify how advice or suggestions from rehabilitation professionals affect self-assessment by care managers. [Participants and Methods] This was a cross-sectional study in which a survey was administered to care managers from in-home care support offices in nine randomly selected municipalities. The survey was used to self-assess how the advice and suggestions from rehabilitation professionals affected the participant's care management process. [Results] Responses were received from 419 participants (response rate 11.3%). Of these responses, 388 (92.6% valid response rate) were analyzed, which revealed that 349 (89.9%) participants had received support from a rehabilitation professional, while 39 (10.1%) had not. Participants who had received support from a rehabilitation professional had significantly higher self-assessment scores than those who had not. Univariate and multiple regression analyses revealed that the factors affecting the self-assessment score were as follows: community care conferences as a support system was a negative factor and years of experience as a care manager was a positive factor. [Conclusion] Advice and suggestions from rehabilitation professionals affect improved care managers' self-assessment scores.

X-ray zooming optics for analyzer-based multi-contrast computed tomography.

An X-ray analyzer-based optics with a zoom function is proposed for observing various samples with apparent-absorption contrast, phase contrast and scattering contrast. The proposed X-ray optics consists of a collimator crystal and an analyzer crystal arranged in a nondispersive (+, -) geometry with a sample placed between them. For the implementation of the zoom function, an asymmetrically cut crystal in the rotated-inclined geometry was used for the analyzer. Proof-of-principle experiments were performed at the vertical wiggler beamline BL-14B of the Photon Factory. First, the magnification was set to 1×, and then it was zoomed into the optimal magnification (10×). At these magnifications, tri-modal contrast cross-sectional images of a sample were obtained by computed tomography. It was confirmed that the image quality at 10× was superior to that at 1×. This achievement opens up new possibilities for observing an entire sample or regions of interest within a sample at optimal magnification, and is expected to be useful for materials science, condensed matter physics, archeology and biomedical science.

Lipophilic Vitamin E Diffusion through Bicontinuous Microemulsions.

We studied the diffusion properties of lipophilic vitamin E (VE) through bicontinuous microemulsions (BME) using both electrochemical and fluorescence correlation spectroscopy (FCS) measurements. We investigated the effect of different composition ratios of micro-water and micro-oil phases in BMEs (W/OBME). When we employed the BME with a lower W/OBME value of 40/60 (oil-rich BME) as an electrolyte solution, we obtained a larger current response from VE at a fluorinated nanocarbon film electrode. Further voltammetric studies revealed that a higher VE diffusion coefficient was observed in the oil-rich BME. The FCS results also exhibited faster diffusion through the oil-rich BME, which played a significant role in accelerating the VE diffusion probably due to the widening of the micro-oil phase pathway in the BME. Moreover, the effect of increasing the VE diffusion was pronounced at the interface between the electrode surface and the BME solution. These results indicate that controlling the conditions of the BME as the measurement electrolyte is very effective for achieving superior electrochemical measurements in a BME.

The efficacy of prophylactic clip closure of mucosal defects after colorectal endoscopic submucosal dissection on delayed bleeding.

OBJECTIVE: Although prophylactic clip closure after endoscopic mucosal resection may prevent delayed bleeding, information regarding colorectal endoscopic submucosal dissection (CR-ESD) is lacking. Therefore, this study evaluated the effect of prophylactic clip closure on delayed bleeding rate after CR-ESD. MATERIALS AND METHODS: A total of 614 CR-ESD procedures performed in 561 patients were retrospectively reviewed. The primary outcome, which was delayed bleeding rate, was analyzed between the prophylactic clip closure and non-closure groups. Furthermore, the predictors of delayed bleeding were also evaluated. RESULTS: The patients were divided into the clip closure group (n = 275) and non-closure group (n = 339). Delayed bleeding rate was significantly lower in the closure group than in non-closure group (6 cases [2.2%] vs. 20 cases [5.9%], p = .026). The univariate logistic regression analyses revealed that delayed bleeding was significantly associated with laterally spreading tumor-granular-nodular mixed type (LST-G-Mix; odds ratio [OR], 3.77; 95% confidence interval [CI], 1.70-8.34; p = .001). By contrast, prophylactic clip closure was significantly associated with low delayed bleeding rate (OR, 0.36; 95%CI, 0.14-0.90; p = .029). The multivariate logistic regression analyses revealed LST-G-Mix as a significant independent delayed bleeding predictor (OR, 3.25; 95%CI, 1.45-7.32; p = .004), whereas, prophylactic clip closure was identified as a significant independent preventive factor of delayed bleeding (OR, 0.39; 95%CI, 0.15-1.00; p = .049). CONCLUSIONS: Prophylactic clip closure after CR-ESD is associated with low delayed bleeding rate. LST-G-Mix promotes delayed bleeding, and performing prophylactic clip closure may be advisable.

Short-term ubiquinol-10 supplementation alleviates tissue damage in muscle and fatigue caused by strenuous exercise in male distance runners.

Background: Coenzyme Q10 (CoQ10) is the electron transporter in oxidative phosphorylation and an endogenous antioxidant. Recent researches have indicated that doses of 200-300 mg/day are needed to recognize effects to prevent oxidative damage in athletes, and the reduced form of CoQ10, ubiquinol-10, is more bioavailable than its oxidized form. Therefore, we hypothesized that higher doses of ubiquinol-10 could elevate plasma CoQ10 levels rapidly and exert physiological benefits in athletes. Therefore, a placebo controlled, double blinded test was carried out to determine the effects of ubiquinol-10 on the extravasate enzymes and fatigue levels of distance runners. Methods: Sixteen male collegiate distance runners were allocated to two groups receiving 300 mg/day of ubiquinol-10 (19.8 ± 1.7 years) or a placebo (20.1 ± 1.6 years) for 12 days during summer training that comprised 25- and 40-km runs on days 7 and 9, respectively. Results: Ubiquinol-10 elevated plasma CoQ10 concentration to 5.62 µg/mL and significantly decreased activities of the serum extravasate enzymes, CK, ALT, LDH (P < 0.01), and AST (P < 0.05) on day 6. Subjective fatigue status was significantly elevated on day 10 (the day after the 45-km run) in the placebo group (P < 0.001), but did not significantly change in the group given ubiquinol-10. Therefore, ubiquinol-10 could mitigate tissue damage and alleviate fatigue status in distance runners during summer training. Conclusions: Ubiquinol-10 (300 mg/day) supplementation elevated plasma CoQ10 concentrations almost to plateau levels, decreased extravasate enzymes within six days, and suppressed the subjective fatigue in male distance runners.

Development of Lectin Modified Fluorescent Magnetic Particles for Highly Sensitive Detection of Glycoconjugates.

I conducted this study to develop an improved method for glycome detection using fluorescent magnetic beads, whose surfaces were modified using lectins, for the highly sensitive detection of saccharides or glycoproteins via fluorescence quenching using a novel fluorescence emitter and quencher pair. The emitter (Cy3 fluorophore) was incorporated into magnetic beads, and a fluorescence quencher (cyanopyranyl group) was bound to glycomes via covalent bonding. The fluorescence intensities of fluorescent magnetic beads containing lectins decreased specifically in the presence of glycomes, which was a result of fluorescence quenching from Cy3 to cyanopyranyl groups due to the formation of a stable complex between lectins and glycome. Fluorescence intensities were plotted as a function of glycoprotein concentration, and good linear relationships were observed. This method enabled the fluorescent reading-out of a series of lectin-glycome interactions on the basis of recognition selectivity and affinity of immobilized lectins without tedious washing processes. Moreover, a simple profiling process was performed using this assay for diverse glycoconjugates, which not only included simple saccharides but also glycoproteins and glycome in cell lysates. These results clearly indicate that the combination of magnetic beads with the novel emitter-quencher pair enabled the highly sensitive detection of lectin-glycome interactions.

Factors affecting the interest of rehabilitation professionals indirectly supporting preventive care projects.

[Purpose] To identify the factors affecting the interest of rehabilitation professionals who indirectly support preventive care projects. [Participants and Methods] Rehabilitation professionals (physical therapists, occupational therapists, and speech-language-hearing therapists) working in 617 hospitals and other health facilities in A Prefecture, Japan. On the basis of their degree of interest in the activities of their respective preventive care projects, the professionals were classified into three groups after evaluating their responses to a self-reporting questionnaire (1,851 parts in total). The subsequent comparisons were performed among the three groups and their responses to the remaining questions. [Results] Analysis of the responses provided by 354 of the 374 rehabilitation professionals who answered the questionnaire revealed the following factors affecting their degree of interest in the preventive care projects indirectly supported by them: advanced age; abundant years of experience practicing; being speech-language-hearing-therapists; experience in post-graduate training; and considering the scope of support as a part of the community. Furthermore, the vast majority of individuals in the group showing superior interest had experience in activities related to indirect support. [Conclusion] Confirmation of the extent to which indirect support by rehabilitation professionals is effective for preventive care services is essential, since such support is difficult to demonstrate, unlike direct support.

Methods for dynamic synchrotron X-ray respiratory imaging in live animals.

Small-animal physiology studies are typically complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron and compact light sources. This group has extensive experience in these types of studies at the SPring-8 and Australian synchrotrons, as well as the Munich Compact Light Source. These experimental settings produce unique challenges. Experiments are always performed in an isolated radiation enclosure not specifically designed for live-animal imaging. This requires equipment adapted to physiological monitoring and test-substance delivery, as well as shuttering to reduce the radiation dose. Experiment designs must also take into account the fixed location, size and orientation of the X-ray beam. This article describes the techniques developed to overcome the challenges involved in respiratory X-ray imaging of live animals at synchrotrons, now enabling increasingly sophisticated imaging protocols.

Learning curve for endoscopic submucosal dissection of early colorectal neoplasms with a monopolar scissor-type knife: use of the cumulative sum method.

OBJECTIVE: Although scissor-type knives such as the Stag-Beetle (SB) Knife Jr are expected to result in a safe and easy colorectal endoscopic submucosal dissection (CR-ESD), information regarding the learning curve is lacking. Therefore, this study evaluated the learning curve with using SB Knife Jr. MATERIALS AND METHODS: We retrospectively reviewed 507 CR-ESD procedures performed in 464 patients using SB Knife Jr. The primary endpoint was a learning curve to achieve a satisfactory complete resection rate. The secondary endpoints were learning curves to achieve a satisfactory en bloc resection rate, curative resection rate, and resection speed. RESULTS: The complete, en bloc, and curative resection rates were 91.9%, 95.9%, and 84.0%, respectively. Moving average analysis showed that 39 cases were required for a complete resection rate of >80%, 41 for an en bloc resection rate of >90%, and 50 for a curative resection rate of >75%. We divided the procedure into three phases using the cumulative sum method: I, II, and III (cases 1-36, 37-119, and 120-507, respectively). Although we found no significant between-phase differences, the complete resection rate showed an increasing trend in Phase III (83.3 vs. 89.2 vs. 93.3%; p = .099). The en bloc resection rate (91.7 vs. 91.6 vs. 97.2%; p = .047) and resection speed (20.5 vs. 7.2 vs. 6.8 min/cm2; p < .001) were greater in Phase III. Despite the larger specimen size (27.3 vs. 38.2 vs. 40.4 mm; p < .001) and more severe fibrosis (p < .001) in Phase III, the procedure time was shorter (73.8 vs. 57.8 vs. 54.2 min; p = .041). The curative resection rate was not significantly different between phases. CONCLUSIONS: SB Knife Jr enables safe and easy CR-ESD during the introductory period compared to the conventional tip-type knife and has an acceptable learning curve. Therefore, using this knife will encourage the widespread adoption of CR-ESD in Asian general hospitals and non-Asian countries.

Hard x-ray phase-contrast microscopy using a Gabor hologram without a zero-order term.

In order to achieve a nanometer-scale resolution in an x-ray microscopy system, a Gabor-type hologram was produced by eliminating the zero-order term of the object diffraction pattern. In this system, a Fresnel zone plate was used for strong illumination of an object, and the zero-order diffraction was physically eliminated by a center stop. An accurate phase plate of π/2 in the Zernike method was numerically created, and the phase-contrast image was realized. The theoretical resolution was 19.8 nm. We proved that a gold nanocube with a size of 50 nm can be reconstructed with the predicted resolution.

Development of Magnetic Nanobeads Modified by Artificial Fluorescent Peptides for the Highly Sensitive and Selective Analysis of Oxytocin.

We describe two novel fluorescent peptides (compounds 1 and 2) targeting oxytocin with a boron-dipyrromethenyl group as the fluorophore bound to an artificial peptide based on the oxytocin receptor, and their application for the analysis of oxytocin levels in human serum using nanometer-sized magnetic beads modified by fluorescent peptides (FMB-1 and FMB-2). Under the optimized experimental protocols, FMB-1 and FMB-2 emitted low levels of fluorescence but emitted much higher levels of fluorescence when associated with oxytocin. The detection limit of oxytocin by FMB-2 was 0.4 pM, which is approximately 37.5 times higher than that of conventional methods, such as ELISA. Using these fluorescent sensors, oxytocin was specifically detected over a wide linear range with high sensitivity, good reusability, stability, precision, and reproducibility. This fluorescent sensor-based detection system thus enabled the measurement of oxytocin levels in human serum, which has widespread applications for oxytocin assays across varied research fields.

Development of Neutral pH-Responsive Microgels by Tuning Cross-Linking Conditions.

Polymer microgels that respond in a range of neutral pH can be useful for the development of molecular imaging tools and drug-delivery carriers. Here, we describe a simple approach in developing microgels that undergo volume phase transitions and substantial nuclear magnetic resonance (NMR) relaxometric changes within a narrow pH range of 6.4 to 7.4. The pH-responsive microgels were synthesized using methacrylic acid and a series of ethylene glycol dimethacrylate cross-linkers with repeating units of ethylene glycol that range from one to four. NMR relaxometry demonstrated that the transverse relaxation time (T2) of a suspension containing microgels that were cross-linked with diethylene glycol dimethacrylate sharply decreases at the pH where volume phase transition occurs. The polymer microgels cross-linked with 40 and 45 mol% of diethylene glycol dimethacrylate caused about 50% T2 reduction with decreasing pH from 6.8 to 6.4. These results demonstrated that responses of microgels to a range of neutral pH can be easily tuned by using appropriate cross-linkers with certain cross-linking degree. This approach can be useful in developing highly sensitive molecular sensors for magnetic resonance imaging (MRI) of tissue pH values.

[Primary leptomeningeal lymphoma with oculomotor paralysis as the initial presentation].

An 85-year-old man presented with right eye ptosis and visual abnormalities. Due to a lack of abnormal findings on plain magnetic resonance imaging (MRI) and laboratory examination, prednisolone therapy was initiated, and ocular myasthenia gravis and ocular symptoms subjectively improved. However, anorexia and conscious disorder appeared during the same period, and he was hospitalized for scrutiny. After admission, left eye adduction disorder and bilateral abduction nerve paralysis were also observed. Enhanced MRI revealed cranial nerve and leptomeninx enhancement. Subsequently, the patient developed seizures and died on the 10th day of hospitalization without being diagnosed. An autopsy revealed infiltration of B-cell lymphoma cells into the subarachnoid space, particularly in the parietal lobe. Similar infiltration was observed in the cerebellum, brainstem, spinal cord, and bilateral oculomotor nerve. Primary leptomeningeal lymphoma is a rare form of primary central nervous system lymphoma without simultaneous parenchymal brain lesions. Clinicians should be aware of this form of lymphoma and carefully monitor its possible occurrence, even when patients are already being treated for other neurological diseases.

Effects of Early Initiation of Solid Versus Liquid Diet after Endoscopic Submucosal Dissection on Quality of Life and Postoperative Outcomes: A Prospective Pilot Randomized Controlled Trial.

BACKGROUND/AIMS: Feeding recommendations after endoscopic submucosal dissection (ESD) for gastric neoplasms are not established and based on clinical experience. METHODS: This was a prospective pilot randomized controlled trial. Patients undergoing ESD for gastric neoplasms were randomly assigned to solid (n = 50) or liquid diet (n = 50) groups. Beginning the day after hemostasis confirmation until discharge, the solid diet group started on a diet of rice porridge, whereas the liquid diet group started on a liquid diet, with gradual transition to solid food. The primary endpoint was delayed bleeding rate. The secondary endpoints were quality of life (QOL), ulcer-stage, hospital fees, and post-ESD symptoms. RESULTS: Delayed bleeding occurred in the solid diet group (2%) but not in the liquid diet group. The QOL evaluation using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-STO22 showed better score in the solid diet group. The patients who felt dietary restriction at discharge was of a larger number in the liquid diet group (p = 0.019). More patients experienced appetite loss (p = 0.038), constipation (p = 0.022), and dietary restriction (p = 0.037) in the liquid diet group during hospitalization. The other endpoints were equivalent between the groups. CONCLUSION: Early initiation of solid foods after ESD is feasible and associated with higher QOL, potentially rendering conventional liquid diets unnecessary, although additional studies are needed (Trial registration number: UMIN000013297).

A combination of oral L-citrulline and L-arginine improved 10-min full-power cycling test performance in male collegiate soccer players: a randomized crossover trial.

PURPOSE: Oral L-citrulline (Cit) increases plasma L-arginine (Arg) concentration and the production of nitric oxide (NO). NO dilates blood vessels and potentially improves sports performance. The combination of oral Arg and Cit (Arg + Cit) immediately and synergistically increases plasma Arg and nitrite/nitrate (NOx) concentrations more than either Cit or Arg alone. This prompted us to assess the effects of oral Arg + Cit on 10-min cycling performance in a double-blind, randomized, placebo-controlled crossover trial. METHODS: Twenty-four male soccer players ingested either Cit + Arg or placebo (both 1.2 g/day each) for 6 days. On day 7, they ingested Cit + Arg 1 h before performing a 10-min full-power pedaling test on a bicycle ergometer. Plasma NOx and amino acid levels were measured before and after the test, as well as the participants' subjective perception of physical exertion. RESULTS: Power output was significantly greater with Cit + Arg than in the placebo group (242 ± 24 vs. 231 ± 21 W; p < 0.05). Plasma concentrations of post-exercise NOx (p < 0.05), Cit (p < 0.01) and Arg (p < 0.01) were significantly higher in the Cit + Arg than in the placebo group, whereas exercise upregulated plasma NOx concentrations in both groups (p < 0.05). Cit + Arg also gave improved post-exercise subjective perception of "leg muscle soreness" and "ease of pedaling" (both p < 0.05). CONCLUSION: Seven days of oral Citrulline (1.2 g/d) and Arginine (1.2 g/d) ingestion improved 10-min cycling performance and the perception of physical exertion in male collegiate soccer players.

Development of Fluorescent Reagent Based on Ligand Exchange Reaction for the Highly Sensitive and Selective Detection of Dopamine in the Serum.

A new fluorescent probe (BDP-Fe2+) was developed for targeting dopamine, with a boron-dipyrromethenyl (BDP) group as the fluorophore and a Fe2+ complex as the ligand exchange site. The free form of BDP-Fe2+ in solution displayed weak fluorescence emission, while it showed strong fluorescence emission after interaction with dopamine due to the release of Fe2+ from BDP-Fe2+, confirming the binding of Fe2+ to dopamine. The increase in fluorescence intensity was concentration-dependent, and a good linear relationship was observed between the fluorescence intensity and dopamine concentration. The detection limit of dopamine by BDP-Fe2+ was 1.1 nM, indicating a 20-fold higher sensitivity than that of previously reported compounds. The reaction of BDP-Fe2+ with dopamine was not affected by the presence of foreign substances, allowing the highly selective detection of dopamine in the human serum sample. The results of this study indicate that the novel compound BDP-Fe2+ is a reliable fluorescent molecular probe for the detection of dopamine and can be widely employed in diverse scientific areas.

Wavelet processing and digital interferometric contrast to improve reconstructions from X-ray Gabor holograms.

In this work, the application of an undecimated wavelet transformation together with digital interferometric contrast to improve the resulting reconstructions in a digital hard X-ray Gabor holographic microscope is shown. Specifically, the starlet transform is used together with digital Zernike contrast. With this contrast, the results show that only a small set of scales from the hologram are, in effect, useful, and it is possible to enhance the details of the reconstruction.