Establishment of indicator for screening of child abuse and neglect in primary school-age children.

AIM: In Japan, elementary schools are committed to early discovery of child abuse and neglect. Under Japanese law, dentists are required to be involved in child welfare and early detection of child abuse. However, the extent to which dental practitioners cooperate for prevention of child abuse with schools remains limited to date. Therefore, we undertook a community-based project that aimed to develop screening indicators to identify potentially abused children based on their oral health condition and behavioural characteristics in education settings. We have already reported on the relationship between oral health condition and child abuse. The present study established an indicator that can facilitate identification and prevention of child abuse/neglect. METHODS: Study design: Cross-sectional study. Questionnaires were given to teachers at an elementary school to ascertain behavioural characteristics observed in children who experienced abuse. CONCLUSION: We developed a check sheet for proper assessment, which requires as little effort as possible, and an index for screening children in need based on teaching staff's observation of students' daily behaviour in school settings. Highly selected items are advantageous as they lead to a decrease in non-response or responses, which can help in improving the accuracy of the response to each question.

MR Imaging Findings of Carcinoma Ex Pleomorphic Adenoma Related to Extracapsular Invasion and Prognosis.

BACKGROUND AND PURPOSE: MR imaging can reflect the pathologic progression of carcinoma ex pleomorphic adenoma (CXPA). This study aimed to identify the imaging findings related to extracapsular invasion of CXPA. Additionally, the pathologic background of these findings was investigated. MATERIALS AND METHODS: This retrospective study included 37 patients with histologically confirmed CXPA. Three radiologists independently evaluated whether the CXPA showed the following characteristic MR imaging findings: border, capsule, the corona sign on fat-saturated T2WI and contrast-enhanced fat-saturated T1WI, and the black ring sign. The corona sign appeared larger on fat-saturated and/or contrast-enhanced fat-saturated T1WI than on T1WI. The black ring sign was defined as an intratumoral nodule with a thick low-intensity rim on T2WI. Interreader agreement of the visual assessment was performed using κ analysis, and MR imaging and histopathologic findings were also correlated. Kaplan-Meier survival and the log-rank test were used to estimate the 3-year disease-free survival. RESULTS: MR imaging findings, especially peritumoral findings, showed a significant difference between invasive and noninvasive CXPA. The reliability was poor for the border and capsule. In contrast, it was good for the corona sign on fat-saturated and contrast-enhanced fat-saturated T1WI and the black ring sign. Pathologically, the corona sign reflected the invasiveness of the tumor and inflammatory cells, while the black ring sign reflected hyalinization or fibrosis. The corona sign also showed a significant difference in the 3-year disease-free survival. CONCLUSIONS: MR imaging findings, including the corona and black ring signs, reliably differentiated invasive and noninvasive CXPA. The corona sign can be used as a prognostic factor for CXPA.

Discharge characteristics of steady-state high-density plasma source based on cascade arc discharge with hollow cathode.

We developed a steady-state high-density plasma source by applying a hollow cathode to a cascade arc discharge device. The hollow cathode is made of a thermionic material (LaB6) to facilitate plasma production inside it. The cascade arc discharge device with the hollow cathode produced a stationary plasma with an electron density of about 1016 cm-3. It was found that the plasma source produces a strong pressure gradient between the gas feed and the vacuum chamber. The plasma source separated the atmospheric pressure (100 kPa) and a vacuum (100 Pa) when the discharge was performed with an argon gas flow rate of 5.0 l/min and a discharge current of 40 A. An analysis of the pressure gradient along the plasma source showed that the pressure difference between the gas feed and the vacuum chamber can be well described by the Hagen-Poiseuille flow equation, indicating that the viscosity of the neutral gas is the dominant factor for producing this pressure gradient. A potential profile analysis suggested that the plasma was mainly heated within cylindrical channels whose inner diameter was 3 mm. This feature and the results of the pressure ratio analysis indicated that the temperature, and, thus, viscosity, of the neutral gas increased with the increasing number of intermediate electrodes. The discharge characteristics and shape of the hollow cathode are suitable for plasma window applications.

Loss of IκBζ Drives Dentin Formation via Altered H3K4me3 Status.

Enforced enrichment of the active promoter marks trimethylation of histone H3 lysine 4 (H3K4me3) and acetylation of histone H3 lysine 27 (H3K27ac) by inhibiting histone demethylases and deacetylases is positively associated with hard tissue formation through the induction of osteo/odontogenic differentiation. However, the key endogenous epigenetic modulator of odontoblasts to regulate the expression of genes coding dentin extracellular matrix (ECM) proteins has not been identified. We focused on nuclear factor (NF)-κB inhibitor ζ (IκBζ), which was originally identified as the transcriptional regulator of NF-κB and recently regarded as the NF-κB-independent epigenetic modulator, and found that IκBζ null mice exhibit a thicker dentin width and narrower pulp chamber, with aged mice having more marked phenotypes. At 6 mo of age, dentin fluorescent labeling revealed significantly accelerated dentin synthesis in the incisors of IκBζ null mice. In the molars of IκBζ null mice, marked tertiary dentin formation adjacent to the pulp horn was observed. Mechanistically, the expression of COL1A2 and COL1A1 collagen genes increased more in the odontoblast-rich fraction of IκBζ null mice than in wild type in vivo, similar to human odontoblast-like cells transfected with small interfering RNA for IκBζ compared with cells transfected with control siRNA in vitro. Furthermore, the direct binding of IκBζ to the COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked by H3K4me3. Based on whole-genome identification of H3K4me3 enrichment, ECM and ECM organization-related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the upregulation of these genes. Collectively, this study suggested that IκBζ is the key negative regulator of dentin formation in odontoblasts by inhibiting dentin ECM- and ECM organization-related gene expression through an altered local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for epigenetically improving the clinical outcomes of dentin regeneration therapies such as pulp capping.

Bayesian inference of ion velocity distribution function from laser-induced fluorescence spectra.

The velocity distribution function is a statistical description that connects particle kinetics and macroscopic parameters in many-body systems. Laser-induced fluorescence (LIF) spectroscopy is utilized to measure the local velocity distribution function in spatially inhomogeneous plasmas. However, the analytic form of such a function for the system of interest is not always clear under the intricate factors in non-equilibrium states. Here, we propose a novel approach to select the valid form of the velocity distribution function based on Bayesian statistics. We formulate the Bayesian inference of ion velocity distribution function and apply it to LIF spectra locally observed at several positions in a linear magnetized plasma. We demonstrate evaluating the spatial inhomogeneity by verifying each analytic form of the local velocity distribution function. Our approach is widely applicable to experimentally establish the velocity distribution function in plasmas and fluids, including gases and liquids.

Conceptual design of heavy ion beam probes on the PLATO tokamak.

Heavy ion beam probe (HIBP) systems have been designed for the new tokamak, PLATO [A. Fujisawa, AIP Conf. Proc. 1993, 020011 (2018)]. The designs have been completed, and the installations are in progress. Two HIBPs are being installed in toroidal sections 180° apart to investigate long-range correlations in the toroidal direction. Each HIBP consists of an injection beamline and a detection beamline as usual. Yet, one of the HIBPs is equipped with an additional detection beamline; the measurement positions of its two detection beamlines can be placed on almost the same magnetic surface yet at poloidal angles that differ by ∼180°. The use of three detection beamlines allows us to investigate spatial asymmetry and long-range correlations in both the toroidal and poloidal directions, simultaneously. The detected beam intensity is expected to be enough for turbulence measurements in almost the entire plasma region when the electron density is up to 1 × 1019 m-3 by selecting appropriate ion species for the probe beam. Each detector has three channels 10 mm apart, allowing measurement of local structures of micro-scale turbulence. Therefore, using the HIBPs on the PLATO tokamak will enable both local and global properties of plasma turbulence to be investigated, simultaneously.

Measurements of radial profile of isotope density ratio using bulk charge exchange spectroscopy.

A bulk charge exchange spectroscopy (BCXS) system using a grism (grating prism) spectrometer has been applied to measure the profile of the deuterium (D) fraction in deuterium and hydrogen (H) mixture plasma in the Large Helical Device. The observed spectrum can be fitted with four Gaussian functions successfully by reduction of free parameters for the least-squares fit. The plasma flow velocity and ion temperature profile measured by charge exchange spectroscopy using carbon impurity are used for estimation of the wavelength shift of hot components to reduce the free parameter. The ion temperature is used to estimate the apparent wavelength shift due to the energy dependent emission cross section only and is not used to set the Doppler width for H and D in the fitting. The sensitivity of the evaluated D fraction on the velocity is increased for a higher D fraction. The error of the D fraction is calculated from the error in the fitted parameter and sensitivity on the velocity of the hot component. The difference in the profile and time trace of the D fraction with D pellet and H pellet injection was observed clearly by BCXS using a grism spectrometer.

Ivermectin reduces in vivo coronavirus infection in a mouse experimental model.

The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.

Tomography system for two-dimensional observation of fluctuation in magnetized plasma.

A tomography system is developed for observing local fluctuations, pursuing higher spatial resolution, over the entire plasma of a linear cylindrical plasma. The system is equipped with totally 126 lines-of-sight that are distributed equally to six sets of light guide arrays placed around the plasma. The system has succeeded in measuring the two-dimensional structure of plasma emission and resolving coherent fluctuation structures, with spatial resolution comparable to the ion Larmor radius.

Transition between Isotope-Mixing and Nonmixing States in Hydrogen-Deuterium Mixture Plasmas.

The transition between isotope-mixing and nonmixing states in hydrogen-deuterium mixture plasmas is observed in the isotope (hydrogen and deuterium) mixture plasma in the Large Helical Device. In the nonmixing state, the isotope density ratio profile is nonuniform when the beam fueling isotope species differs from the recycling isotope species and the profile varies significantly depending on the ratio of the recycling isotope species, although the electron density profile shape is unchanged. The fast transition from nonmixing state to isotope-mixing state (nearly uniform profile of isotope ion density ratio) is observed associated with the change of electron density profile from peaked to hollow profile by the pellet injection near the plasma periphery. The transition from nonmixing to isotope-mixing state strongly correlates with the increase of turbulence measurements and the transition of turbulence state from TEM to ion temperature gradient is predicted by gyrokinetic simulation.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Measurements of radial profile of hydrogen and deuterium density in isotope mixture plasmas using bulk charge exchange spectroscopy.

A bulk charge exchange spectroscopy system has been applied to measure the radial profiles of the hydrogen (H) and deuterium (D) density ratio in the isotope mixture plasma in a large helical device. Charge exchange lines of Hα and Dα are fitted by 4 Gaussian of H and D cold components and H and D hot components with 5 parameters by combining the measurement of plasma toroidal rotation velocity with carbon charge exchange spectroscopy. The radial profiles of the relative density of hydrogen and deuterium ions are derived from H and D hot components measured and the beam density calculated from beam attenuation calculation. A proof-of-principle experiment is performed by the H pellet and the D pellet injections into the H-D mixture plasma.

A proposal of Fourier-Bessel expansion with optimized ensembles of bases to analyse two dimensional image.

It is a critical issue to find the best set of fitting function bases in mode structural analysis of two dimensional images like plasma emission profiles. The paper proposes a method to optimize a set of the bases in the case of Fourier-Bessel function series, using their orthonormal property, for more efficient and precise analysis. The method is applied on a tomography image of plasma emission obtained with the Maximum-likelihood expectation maximization method in a linear cylindrical device. The result demonstrates the excellency of the method that realizes the smaller residual error and minimum Akaike information criterion using smaller number of fitting function bases.

Efficacy and safety of brodalumab in patients with generalized pustular psoriasis and psoriatic erythroderma: results from a 52-week, open-label study.

BACKGROUND: A T-helper (Th) cell subset Th17 preferentially produces interleukin (IL)-17 and plays a pivotal role in the pathogenesis of psoriasis. However, the pathological roles of IL-17 cascades in generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE) have not been well established. OBJECTIVES: To evaluate the efficacy and safety of brodalumab, a human immunoglobulin G2 monoclonal antibody against human IL-17-receptor A (IL-17RA), in Japanese patients with GPP and PsE. METHODS: This was an open-label, multicentre, long-term phase III study in Japanese patients with rare and severe types of psoriasis. Patients received brodalumab 140 mg at day 1 and weeks 1 and 2, and then every 2 weeks until week 52. The primary endpoint was the Clinical Global Impression of Improvement (CGI). Safety evaluations included treatment-emergent adverse events (AEs) and changes in laboratory parameters. RESULTS: A total of 12 patients with GPP and 18 with PsE were enrolled. Ten patients with GPP and 16 with PsE completed the study. At week 52 (last observation carried forward), CGI remission or improvement was achieved in 11 patients with GPP and 18 with PsE. The most commonly reported AE was nasopharyngitis (33·3%). Five serious AEs occurred during the study. However, none was considered treatment-related. CONCLUSIONS: Brodalumab significantly improved the symptoms of patients with GPP and PsE throughout the 52 weeks, and demonstrated favourable safety profiles without any new safety signals. Inhibition of IL-17RA-mediated signalling by brodalumab is expected to be a promising new treatment option for patients with GPP and PsE.

Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-α antagonist treatment using a novel interleukin-8 reporter cell line.

BACKGROUND: Tumour necrosis factor (TNF)-α antagonist therapy is currently used for moderate and severe psoriasis. However, this treatment has several drawbacks, including interindividual variability in clinical response and secondary loss of effectiveness. OBJECTIVES: To evaluate quantitatively the TNF-α-neutralizing activity of the plasma of patients with psoriasis during TNF-α antagonist therapy and to determine poor responders objectively. METHODS: We used a human interleukin-8 reporter monocyte cell line, THP-G8, that harbours a stable luciferase orange (SLO) gene under the control of the interleukin-8 promoter. After confirming its dose-dependent response to exogenous TNF-α, we examined the suppressive activity of TNF-α antagonists and of the patients' plasma during TNF-α antagonist therapy on TNF-α-induced SLO luciferase activity (TNF-SLO-LA). RESULTS: Pretreatment of TNF-α with TNF-α antagonists or with the plasma of patients with psoriasis who achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) dose dependently suppressed TNF-SLO-LA. There was a significant correlation between change in PASI and percentage suppression (inhibitory rate of a 1 : 2 dilution of patient plasma on TNF-SLO-LA). A percentage suppression of 50·3% has a positive predictive value of 87% of achieving PASI 75, with a sensitivity of 93% and a specificity of 80%. CONCLUSIONS: Therapeutic monitoring of patients with psoriasis during TNF-α antagonist therapy using THP-G8 can provide a useful tool to determine objectively the efficacy of the administered TNF-α antagonists.

The spectrophotometrical analysis of rhododendrol-induced leucoderma using a novel multispectral camera.

BACKGROUND: Many users in Japan of skin brightening/lightening cosmetics containing rhododendrol (RD) have developed leucoderma. Leucoderma appears on skin areas repeatedly treated with RD-containing cosmetics. RD-induced leucoderma (RDIL) presents different degrees of well-defined hypopigmentation. It is crucial to determine the degree of hypopigmentation to differentiate RDIL from vitiligo vulgaris (VV). OBJECTIVES: To quantitatively evaluate hypopigmentation of RDIL lesions and the recovery of pigmentation, and to compare the hypopigmentation with VV and normal skin. MATERIALS AND METHODS: Sixteen cases of RDIL, nine cases of VV and 15 healthy controls were examined using a novel multispectral camera (MSC) that can simultaneously obtain the reflection intensity at 10-nm wavelength intervals from 400 to 760 nm of the photographed area. ∆Absorbance was calculated by subtracting the log of reflection intensity of the target area from that of a white reflection standard. RESULTS: Most RDIL lesions showed lower ∆Absorbance than healthy skin and higher ∆Absorbance than VV lesions between 400 and 550 nm. Statistical comparison of the maximum ∆Absorbance from 420 to 460 nm (Max∆Absorbance) for VV, RDIL and control skin showed that the Max∆Absorbance of RDIL was significantly higher than that of VV and lower than that of control skin. The comparison of ∆Absorbance of the same sites in RDIL lesions between the initial visit and 6 months later showed significant improvement after 6 months. CONCLUSIONS: These studies demonstrated quantitative changes in RDIL and its recovery phase and suggested the utility of a MSC in obtaining objective colour information of skin disorders.