Evaluation of large airway specimens obtained by transbronchial lung cryobiopsy in diffuse parenchymal lung diseases.

BACKGROUND: The difference in diagnostic yield between surgical lung biopsy and transbronchial lung cryobiopsy (TBLC) in diffuse parenchymal lung diseases (DPLD) has been reported to be due to differences in the rate of interpathologist agreement, specimen size, and specimen adequacy. In TBLC, the specimens containing large airway components are generally believed as inadequate specimens for histological evaluation, but the detailed characteristics of TBLC specimens including the large airway and the impact on histological diagnostic rates of DPLD have not been investigated. METHODS: We retrospectively reviewed the specimen characteristics of patients with DPLD who underwent TBLC. RESULTS: Between February 2018 and January 2020, 74 patients and 177 specimens were included. There were 85 (48.0%) large airway specimens (LAS) that contained bronchial gland or bronchial cartilage. The ideal specimen ratio was significantly lower in the LAS-positive group than that in the LAS-negative group (5.8% vs. 45.6%), and the proportion of bronchioles, alveoli, and perilobular area were similarly lower in the LAS-positive group. The presence of traction bronchiectasis and diaphragm overlap sign on high-resolution computed tomography (HRCT) were also significantly higher in the LAS-positive group than those in the LAS-negative group. We observed a statistically significant trend in histological diagnostic yield (40.7% in LAS positive group; 60.8% in LAS positive and negative group; 91.6% in LAS negative group) (Cochran-Armitage trend test). CONCLUSION: LAS is a specimen often collected in TBLC and contains a low percentage of bronchioles, alveoli, and perilobular area. Since the histological diagnostic yield tends to be higher in cases that do not contain LAS, it may be important to determine the biopsy site that reduces the frequency of LAS collection by referring to the HRCT findings in TBLC.

High-heat flux ball-pen probe head in ASDEX-Upgrade.

A new high heat flux ball-pen probe head installed on the midplane manipulator is currently being used in ASDEX-Upgrade (AUG). The probe was designed to withstand high heat fluxes making possible the investigation of the plasma edge under harsh conditions, such as low power H-mode. Composed of seven pins (four Langmuir probes, mounted in two Mach probe pairs, and three ball-pen probes), the new probe head allows us to measure several plasma parameters simultaneously and with high temporal resolution. A novel method to correct the sheath potential dynamically accounting for the total secondary electron emission is introduced together with applications to obtain the electron temperature and plasma potential profiles. The total secondary electron emission yield is obtained from particle in cell simulations in AUG condition and probe realistic impact angle with respect to the magnetic field. Finally, the probe capability to investigate turbulence around the separatrix of AUG is discussed.

Linearized spectrum correlation analysis for thermal helium beam diagnostics.

We introduce a new correlation analysis technique for thermal helium beam (THB) diagnostics. Instead of directly evaluating line ratios from fluctuating time series, we apply arithmetic operations to all available He I lines and construct time series with desired dependencies on the plasma parameters. By cross-correlating those quantities and by evaluating ensemble averages, uncorrelated noise contributions can be removed. Through the synthetic data analysis, we demonstrate that the proposed analysis technique is capable of providing the power spectral densities of meaningful plasma parameters, such as the electron density and the electron temperature, even under low-photon-count conditions. In addition, we have applied this analysis technique to the experimental THB data obtained at the ASDEX Upgrade tokamak and successfully resolved the electron density and temperature fluctuations up to 90 kHz in a reactor relevant high power scenario.

Autoimmune pulmonary alveolar proteinosis developed during immunosuppressive treatment in polymyositis with interstitial lung disease: a case report.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant proteins within the alveolar spaces. Autoimmune PAP (APAP) caused by elevated levels of GM-CSF autoantibodies (GM-Ab) is very rarely associated with systemic autoimmune disease. Here we report a case of APAP manifested during immunosuppressive treatment for polymyositis with interstitial lung disease. CASE PRESENTATION: A 52-year-old woman treated at our hospital because of polymyositis with interstitial pneumonia had maintained remission by immunosuppressive treatment for 15 years. She had progressive dyspnea subsequently over several months with her chest CT showing ground-glass opacities (GGO) in bilateral geographic distribution. Her bronchoalveolar lavage fluid with cloudy appearance revealed medium-sized foamy macrophages and PAS-positive amorphous eosinophilic materials by cytological examination. We diagnosed her as APAP due to an increased serum GM-CSF autoantibody level. Attenuating immunosuppression failed to lead GGO improvement, but whole lung lavage (WLL) was effective in her condition. CONCLUSIONS: PAP should be considered as one of the differential diseases when the newly interstitial shadow was observed during immunosuppressive treatment. WLL should be regarded as the treatment option for APAP concurred in connective tissue disease (CTD).

Serum high-mobility group box 1 is correlated with interferon-α and may predict disease activity in patients with systemic lupus erythematosus.

Sensing self-nucleic acids through toll-like receptors in plasmacytoid dendritic cells (pDCs), and the dysregulated type I IFN production, represent pathogenic events in the development of the autoimmune responses in systemic lupus erythematosus (SLE). Production of high-mobility group box-1 protein (HMGB1) promotes type I IFN response in pDCs. To better understand the active pathogenic mechanism of SLE, we measured serum levels of HMGB1, thrombomodulin, and cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, IFNα, IFNγ, TNFα) in 35 patients with SLE. Serum HMGB1 and IFNα were significantly higher in patients with active SLE (SLE Disease Activity Index (SLEDAI) score ≥ 6) compared with healthy donors or patients with inactive SLE. Furthermore, the HMGB1 levels were significantly correlated with IFNα levels. By qualitative analysis, the detection of serum IFNα or HMGB1 suggests active SLE and the presence of SLE-related arthritis, fever, and urinary abnormality out of SLEDAI manifestations. Collectively, HMGB1 and IFNα levels are biomarkers reflecting disease activity, and qualitative analysis of IFNα or HMGB1 is a useful screening test to estimate SLE severity and manifestations. Our results suggest the clinical significance of type I IFNs and HMGB1 as key molecules promoting the autoimmune process in SLE.

Direct Measurement of a Toroidally Directed Zonal Flow in a Toroidal Plasma.

Zonal flow appears in toroidal, magnetically confined plasmas as part of the self-regulated interaction of turbulence and transport processes. For toroidal plasmas having a strong toroidal magnetic field, the zonal flow is predominately poloidally directed. This Letter reports the first observation of a zonal flow that is toroidally directed. The measurements are made just inside the last closed flux surface of reversed field pinch plasmas that have a dominant poloidal magnetic field. A limit cycle oscillation between the strength of the zonal flow and the amplitude of plasma potential fluctuations is observed, which provides evidence for the self-regulation characteristic of drift-wave-type plasma turbulence. The measurements help advance understanding and gyrokinetic modeling of toroidal plasmas in the pursuit of fusion energy.

Development of a multi-channel capacitive probe for electric field measurements with fine spatial and high time resolution.

A capacitive probe [Tan et al., Rev. Sci. Instrum. 88, 023502 (2017)] is one of a few diagnostics that is directly sensitive to the plasma potential. Using this diagnostic technique, a Multi-channel Linear Capacitive Probe (MLCP) is developed for turbulence measurements. The MLCP has 10 spatial channels and provides 9 points of radial electric field measurements simultaneously with a spatial step of 7 mm. A new readout circuit and a correction technique for low frequency attenuation are also developed to achieve the required spatial and time resolution. A performance test of the MLCP using a reversed field pinch plasma confirms that the MLCP resolves sub-centimeter structures of the equilibrium radial electric field profile and fluctuations up to 680 kHz.

Measurements of Impurity Transport Due to Drift-Wave Turbulence in a Toroidal Plasma.

The first direct measurements of an impurity particle flux driven by drift-wave turbulence in a toroidal magnetized plasma are reported. The correlation between the impurity density and radial velocity fluctuations is measured using ion Doppler spectroscopy. The small, very fast radial velocity fluctuation is resolved with the aid of a new linearized spectrum correlation analysis method that rejects uncorrelated noise as the sample size increases. The measured C^{2+} turbulent impurity flux in the edge of the plasma is directed inward and is consistent with impurity density measurements. This is also the first direct evidence for fluctuation-induced transport due to trapped-electron-mode turbulence in reversed field pinch plasmas.

Dependence of Perpendicular Viscosity on Magnetic Fluctuations in a Stochastic Topology.

In a magnetically confined plasma with a stochastic magnetic field, the dependence of the perpendicular viscosity on the magnetic fluctuation amplitude is measured for the first time. With a controlled, ∼ tenfold variation in the fluctuation amplitude, the viscosity increases ∼100-fold, exhibiting the same fluctuation-amplitude-squared dependence as the predicted rate of stochastic field line diffusion. The absolute value of the viscosity is well predicted by a model based on momentum transport in a stochastic field, the first in-depth test of this model.

Linearized spectrum correlation analysis for line emission measurements.

A new spectral analysis method, Linearized Spectrum Correlation Analysis (LSCA), for charge exchange and passive ion Doppler spectroscopy is introduced to provide a means of measuring fast spectral line shape changes associated with ion-scale micro-instabilities. This analysis method is designed to resolve the fluctuations in the emission line shape from a stationary ion-scale wave. The method linearizes the fluctuations around a time-averaged line shape (e.g., Gaussian) and subdivides the spectral output channels into two sets to reduce contributions from uncorrelated fluctuations without averaging over the fast time dynamics. In principle, small fluctuations in the parameters used for a line shape model can be measured by evaluating the cross spectrum between different channel groupings to isolate a particular fluctuating quantity. High-frequency ion velocity measurements (100-200 kHz) were made by using this method. We also conducted simulations to compare LSCA with a moment analysis technique under a low photon count condition. Both experimental and synthetic measurements demonstrate the effectiveness of LSCA.

Absolute wavelength calibration of a Doppler spectrometer with a custom Fabry-Perot optical system.

An Ion Doppler Spectrometer (IDS) is used for fast measurements of C VI line emission (343.4 nm) in the Madison Symmetric Torus. Absolutely calibrated flow measurements are difficult because the IDS records data within 0.25 nm of the line. Commercial calibration lamps do not produce lines in this narrow range. A light source using an ultraviolet LED and etalon was designed to provide a fiducial marker 0.08 nm wide. The light is coupled into the IDS at f/4, and a holographic diffuser increases homogeneity of the final image. Random and systematic errors in data analysis were assessed. The calibration is accurate to 0.003 nm, allowing for flow measurements accurate to 3 km/s. This calibration is superior to the previous method which used a time-averaged measurement along a chord believed to have zero net Doppler shift.

Upgrading a high-throughput spectrometer for high-frequency (<400 kHz) measurements.

The upgraded spectrometer used for charge exchange recombination spectroscopy on the Madison Symmetric Torus resolves emission fluctuations up to 400 kHz. The transimpedance amplifier's cutoff frequency was increased based upon simulations comparing the change in the measured photon counts for time-dynamic signals. We modeled each signal-processing stage of the diagnostic and scanned the filtering frequency to quantify the uncertainty in the photon counting rate. This modeling showed that uncertainties can be calculated based on assuming each amplification stage is a Poisson process and by calibrating the photon counting rate with a DC light source to address additional variation.

Structural changes in dermal collagen and oxidative stress levels in the skin of Japanese overweight males.

OBJECTIVE: It has been reported that obese people have poorly organized dermal collagen structure because of the degradation of collagen fibers, which is caused by an increase in oxidative stress levels associated with the hypertrophy of subcutaneous adipose cells. However, it is unclear whether an increase in oxidative stress levels caused by the accumulation of subcutaneous adipose tissue and a change in the dermal structure also occur in overweight and obese Japanese people. The objectives of this study are to identify structural changes that occur in the dermis and to measure the levels of oxidative stress in Japanese overweight males. METHODS: The overweight group included 43 Japanese male volunteers aged between 25 and 64 years and with a body mass index (BMI) of ≥25 and <30. The control group included 47 male volunteers aged between 22 and 64 years and with BMI of <25. The 20-MHz Dermascan C® ultrasound scanner with software for image analyses was used. Echogenicity of the upper and lower dermis was measured. The mRNA expression level of heme oxygenase-1 (HMOX1) in hair follicles was quantitatively analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and was used as a marker of oxidative stress. Ultrasonographic imaging and collection of hair follicles were performed at the same site on the thigh, abdomen, and upper arm. RESULTS: The HMOX1 mRNA expression level in the abdomen and thigh was significantly lower in the overweight group than in the control group. Moreover, the echogenicity of the upper dermis of the abdomen and the lower dermis of the abdomen and thigh was significantly lower in the overweight group than in the control group. CONCLUSION: We detected an increase in oxidative stress levels and a decrease in the density of dermal collagen at the same site on the thigh, abdomen, and upper arm of Japanese overweight males. These findings suggest the fragility of the dermis of Japanese overweight males, which might have been caused by the accumulation of subcutaneous adipose tissue.

Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia--a multicenter, double-blind, randomized, placebo-controlled study.

BACKGROUND: Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD). METHODS: FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment (GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. KEY RESULTS: Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance (p = 0.09). Epigastric pain was significantly improved (p = 0.04) and postprandial fullness tended to improve (p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. CONCLUSIONS & INFERENCES: Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. (UMIN Clinical Trials Registry, Number UMIN000003954).

Influence of differences in washing methods on skin texture.

OBJECTIVE: The objective of this study was to clarify the effects of different body washing methods on skin texture. METHODS: Subjects were nine healthy women in their 20s. Skin on the inside of the forearms was washed every day for 4 weeks with protective washing (right forearm) and with non-protective washing (left forearm). We performed comparison of the right forearm and the left forearm. For the evaluation of skin texture, the interval of the sulcus cutis, and the mean and variance of the thickness of the sulcus cutis on digitized images were measured. Moreover, the numbers of equilateral triangles consisting of sulcus cutis were counted to evaluate skin texture. RESULTS: From the first week, the interval of sulcus cutis was significantly narrower with protective washing than with non-protective washing. The numbers of equilateral triangles increased significantly more with protective washing than with non-protective washing in weeks 1, 2 and 4. Although this study found no significant difference in mean of the thickness of the sulcus cutis, the interval of sulcus cutis and the number of triangles differed significantly with protective washing. The narrower intervals between sulcus cutis mean finer-textured skin and sulcus cutis are formed by triangles or quadrilaterals, and the more uniform these shapes are, the finer and more regular the texture Therefore, skin texture may have become finer as a result of protective washing. CONCLUSION: These findings suggest that protective washing produces an even skin texture. They also suggest that number of equilateral triangles, as used in this study, may be useful as an index of skin texture.

Field tests of Poly(I:C) immunization with nervous necrosis virus (NNV) in sevenband grouper, Epinephelus septemfasciatus (Thunberg).

It was recently reported that Poly(I:C) immunization with live nervous necrosis virus (NNV) confers protection in sevenband grouper, Epinephelus septemfasciatus (Thunberg), from NNV infection. In the present study, we conducted field tests with sevenband grouper for the evaluation of Poly(I:C) immunization efficacy. In the first experiment, sevenband grouper were immunized with NNV followed by Poly(I:C) administration 7 weeks before natural occurrence of viral nervous necrosis (VNN). Survival rate of the naïve fish was 71.0%, whereas that of the immunized fish was 99.8%. In the second experiment, sevenband grouper were immunized 10 months before VNN occurrence and survival rate of the non-treated and vaccinated fish was 79.5% and 97.5%, respectively. In the third experiment, we administered Poly(I:C) to sevenband grouper at 20 days after natural occurrence of VNN. The survival rate of the non-treated fish was 9.8%, whereas that of fish administered Poly(I:C) was 93.7%. Based on these results, it was concluded that Poly(I:C) immunization conferred protection in fish against NNV infection in field tests and the protection lasted more than 10 months. Furthermore, even after occurrence of VNN, fish mortality could be reduced by Poly(I:C) administration and there was an unexpected curative effect on VNN-affected fish.

Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population.

AIMS/HYPOTHESIS: Resistin is a cytokine derived from adipose tissue and is implicated in obesity-related insulin resistance and type 2 diabetes mellitus. Polymorphisms of the resistin gene (RETN) have been shown to affect the plasma resistin concentration. The aims of this study were to identify polymorphisms of RETN that influence plasma resistin concentration and to clarify the relation between plasma resistin level and metabolic disorders in an aged Japanese cohort. METHODS: The study participants comprised 3133 individuals recruited to a population-based prospective cohort study (KING study). Plasma resistin concentration, BMI, abdominal circumference, blood pressure, fasting plasma glucose and serum insulin concentrations, HbA(1c) content and serum lipid profile were measured in all participants. The HOMA index of insulin resistance (HOMA-IR) was also calculated. Eleven polymorphisms of RETN were genotyped. RESULTS: A combination of ANOVA and multiple linear regression analysis in screening and large-scale subsets of the study population revealed that plasma resistin concentration was significantly associated with rs34861192 and rs3745368 polymorphisms of RETN. Multiple linear regression analysis with adjustment for age and sex also showed that the plasma resistin level was significantly associated with serum concentrations of HDL-cholesterol, triacylglycerol and insulin, as well as with BMI. CONCLUSIONS/INTERPRETATION: Our results implicate the rs34861192 and rs3745368 polymorphisms of RETN as robust and independent determinants of plasma resistin concentration in the study population. In addition, plasma resistin level was associated with dyslipidaemia, serum insulin concentration and obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00262691.

Lymphocystis disease virus persists in the epidermal tissues of olive flounder, Paralichthys olivaceus (Temminch & Schlegel), at low temperatures.

Olive flounder artificially infected with lymphocystis disease virus (LCDV) were reared at 10, 20 and 30 degrees C for 60 days, to compare LCD-incidence. In the fish reared at 20 degrees C, lymphocystis cells appeared on the skin and fins at 35 days post-challenge, and the cumulative LCD-incidence was 80% at 60 days. High levels of LCDV, with a mean polymerase chain reaction (PCR) titre of 10(6) PCR-U mg(-1) tissue, were detected in the fins and skin of LCD-affected fish at 20 degrees C, but were not detected in the spleen, kidney, brain and intestinal tissues of these fish. No LCD clinical signs were observed in the fish reared at 10 degrees C and 30 degrees C; however, a low level of LCDV (10(3) PCR-U mg(-1) tissue) was detected in the fins and skin of these fish. By increasing the rearing temperature from 10 to 20 degrees C, lymphocystis clusters appeared on the skin and fins of the fish with no previous LCD clinical signs within 33 days after the temperature change. It was shown that permissive cells for LCDV infection exist in the epidermis of olive flounder. At low temperatures, small amounts of LCDV were able to persist over a period extended for a further 45 days in the fish epidermis, even though the fish showed no LCD clinical signs. The optimum growth temperature of LCDV is near 20 degrees C.

Non-specific adsorption of fish immunoglobulin M (IgM) to blocking reagents on ELISA plate wells.

Enzyme-linked immunosorbent assay (ELISA) is a popular technique for quantifiable detection of specific antibodies in warm-blooded animals, but it has not been accepted for detection of fish antibodies because of its low reproducibility, which is due in part to high background optical density (OD) measurements. In the present study, we report that the high background of a fish antibody-detection ELISA resulted from non-specific adsorption of fish immunoglobulin M (IgM) to blocking reagents on the ELISA plate wells. Four fish sera (from rainbow trout Oncorhynchus mykiss, masu salmon O. masou, Japanese flounder Paralichthys olivaceus and koi Cyprinus carpio) were poured into ELISA plate wells pre-blocked with several blocking reagents (skim milk, soybean milk, bovine serum albumin, fetal bovine serum, gelatin and Roche BlockingReagent) and then washed out in order to measure the remaining fish IgM on the ELISA plate wells. Significant amounts of fish IgMs (OD absorbance at 492 nm: 0.3 to 1.1) remained on the ELISA plate wells with no antigenic protein except blocking reagents. The amount of remaining fish IgMs on the ELISA plate wells decreased significantly following treatment of fish sera with skim milk. However, the specific immuno-reactivity of fish IgM was not reduced by such treatment. Thus, we conclude that treatment of fish sera with skim milk is useful in reducing the high background OD often observed in fish IgM detection ELISA.