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Abstract Background In patient assessment for recurrence of neoplasia, a biomarker that shows an elevated serum value before the first treatment is a candidate for follow-up examination. The biomarker squamous cell carcinoma antigen is usually utilized for follow-up of squamous cell cancer of the cervix. Case presentation We herein report a 30-year-old Japanese woman of postoperative metastasis of cervical squamous cell cancer to the mediastinal and supraclavicular lymph nodes as indicated by an elevated serum cancer antigen 125 concentration and not by the squamous cell carcinoma antigen value. After chemoradiotherapy and chemotherapy, the serum cancer antigen 125 concentration decreased to a normal value. Squamous cell carcinoma antigen was found to be distributed in both the squamous cell cancer tissue of the cervix and the supraclavicular lymph node metastatic tissue. By contrast, cancer antigen 125 was distributed in the supraclavicular lymph node metastatic tissue but not in the original squamous cell cancer tissue of the cervix. Conclusion In this case, metastasis of cervical cancer to the mediastinal and supraclavicular lymph nodes was shown by the biomarker cancer antigen 125, which was not present in the original neoplasia.

Proton-exchange-membrane hydrogen fuel cells (PEMFCs) are an important energy device for achieving a sustainable hydrogen society. Carbon-based catalysts used in PEMFCs’ cathode can degrade significantly during operation-voltage shifts due to the carbon deterioration. The longer lifetime of the system is necessary for the further wide commercialization of PEMFCs. Therefore, carbon-free catalysts are required for PEMFCs. In this study, highly crystallized conducting Sb-doped SnO2 (Sb-SnO2) nanoparticles (smaller than 7 nm in size) were synthesized using an ozone-assisted hydrothermal synthesis. Pt nanoparticles were loaded on Sb-SnO2 supporting particles by polyol method to be “Pt/Sb-SnO2 catalyst”. The Pt/Sb-SnO2 catalyst showed a high oxygen reduction reaction (ORR) mass activity (178.3 A g−1-Pt @ 0.9 V), compared to Pt/C (149.3 A g−1-Pt @ 0.9 V). In addition, the retention ratio from the initial value of electrochemical surface area (ECSA) during 100,000-voltage cycles tests between 1.0 V and 1.5 V, Pt/SnO2 and Pt/Sb-SnO2 catalyst exhibited higher stability (90% and 80%), respectively, than that of Pt/C catalyst (47%). Therefore, the SnO2 and Sb-SnO2 nanoparticles synthesized using this new ozone-assisted hydrothermal method are promising as carbon-free catalyst supports for PEMFCs.

Objective: To assess the diagnostic performance and calculate the optimal threshold for quantitative biomarkers to differentiate bone metastasis and benign bone marrow lesions using turbo spin echo (TSE) Dixon images with a 3.0 T scanner. Materials and methods: Each 100 patients diagnosed with bone metastases and variable benign bone marrow lesions on spine MRI were included retrospectively. Images included in-phase (IP), opposed-phase (OP), water images (WI), and fat images (FI) by the TSE Dixon technique with T1WI and T2WI using a 3.0 T scanner. Regions of interest (ROI) of the lesions were manually drawn by two musculoskeletal radiologists independently, and the average signal intensity was recorded. The signal reduction rate from IP to OP (%drop) and a fat fraction (%fat) were calculated. Results: All biomarkers showed a significant difference between metastatic and benign lesions (P

Portosystemic shunts with cirrhosis may lead to hepatic encephalopathy (HE), which is often pharmacotherapy-resistant. We report a case of a 66-year-old female patient diagnosed with alcoholic cirrhosis and uncontrolled HE. She underwent percutaneous transhepatic obliteration (PTO) for treatment of a large portosystemic shunt from the left and right gastric veins to the azygos vein. We embolized the target veins using hydro-coated coils and filled them with n-butyl-2-cyanoacrylate (NBCA), leading to firmed obstruction of the large portosystemic shunt without NBCA migration, thus reducing the number of coils required. The HE symptoms improved after PTO and could thereafter be controlled with conservative therapy. Our results showed that PTO using an NBCA injection inside hydrogel-coated coils for a large portosystemic shunt associated with HE is effective and safe.

Objectives Anti-differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis, which has been described as clinically amyopathic dermatomyositis, complicates rapidly progressive interstitial lung disease (ILD). Owing to the absence of significant muscle symptoms, musculoskeletal MRI is often not performed. In this study, we aimed to devise a simple evaluation method using musculoskeletal MRI findings to elucidate the relationship between MRI findings and ILD prognosis and development.Methods The medical records and MRI scans of the proximal muscles at the time of diagnosis were retrospectively reviewed for 28 patients with anti-MDA5 antibody-positive dermatomyositis who were admitted to The Jikei University Hospital and The Jikei University Kashiwa Hospital between January 2008 and March 2022. Three observers evaluated nine proximal muscles for high signals on either short-tau inversion recovery images and/or fat-saturated gadolinium-enhanced T1-weighted images in the fascia and/or in the margins of the muscles in contact with the fascia (fascial pattern), and/or high signals in the muscles away from the fascia (intramuscular pattern), and a consensus was reached.Results Of the 28 patients, 15 presented with ‘radiological myositis’, where an intramuscular pattern was observed at any site. Patients with radiological myositis had significantly higher survival rates than those without radiological myositis, despite the lower rate of triple therapy with prednisolone, calcineurin inhibitors and cyclophosphamide. The spread of ILD on chest CT negatively and significantly correlated with the proportion of intramuscular lesions.Conclusion The detection of intramuscular lesions on musculoskeletal MRI using our novel evaluation method could be clinically useful as a favourable prognostic marker.

Background: To compare the potential of various bone evaluations by considering photon-counting CT (PCCT) and multiple energy-integrating-detector CT (EIDCT), including three dual-energy CT (DECT) scanners with standardized various parameters in both standard resolution (STD) and ultra-high-resolution (UHR) modes. Methods: Four cadaveric forearms were scanned using PCCT and five EIDCTs, by applying STD and UHR modes. Visibility of bone architecture, image quality, and a non-displaced fracture were subjectively scored against a reference EIDCT image by using a five-point scale. Image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also compared. To assess metal artifacts, a forearm with radial plate fixation was scanned by with and without Tin filter (Sn+ and Sn−), and virtual monoenergetic image (VMI) at 120 keV was created. Regarding Sn+ and VMI, images were only obtained from the technically available scanners. Subjective scores and the areas of streak artifacts were compared. Results: PCCT demonstrated significantly lower noise (p < 0.001) and higher bone SNR and CNR (p < 0.001) than all EIDCTs in both resolution modes. However, there was no significant difference between PCCT and EIDCTs in almost all subjective scores, regardless of scan modes, except for image quality where a significant difference was observed, compared to several EIDCTs. Metal artifact analysis revealed PCCT had larger artifact in Sn− and Sn+ (p < 0.001), but fewer in VMIs than three DECTs (p < 0.001 or 0.001). Conclusions: Under standardized conditions, while PCCT had almost no subjective superiority in visualizing bone structures and fracture line when compared to EIDCTs, it outperformed in quantitative analysis related to image quality, especially in lower noise and higher tissue contrast. When using PCCT to assess cases with metal implants, it may be recommended to use VMIs to minimize the possible tendency for artifact to be pronounced.

Abstract Background Endovascular therapy (ET) for delayed hepatic artery post-pancreatectomy hemorrhage (HA-PPH) may require complete hepatic artery occlusion (HAO). Nonetheless, the development of extrahepatic collateral circulation (EHC) and the relationship between radiological factors (EHC, portal vein stenosis, and HAO) and adverse hepatic events after ET remain unclear. This study aimed to evaluate the efficacy and safety of ET for delayed PPH and examine the development of EHC. Methods A total of 19 ET cases for delayed HA-PPH were reviewed. Hepatic adverse events, portal vein stenosis, HAO, and mortality rate after ET were evaluated. Moreover, EHC from the left gastric artery (LGA), right inferior phrenic artery (RIPA), left inferior phrenic artery (LIPA), right internal thoracic artery (RITA), left internal thoracic artery (LITA), renal artery (RA), omental artery (OA), intercostal artery (IA), and branch of superior mesenteric artery (BSMA) was assessed using angiogram and computed tomography angiography (CTA). Results All cases were successfully treated using transcatheter arterial embolization (n = 17) and stent-graft placement (n = 2) without mortality. EHC from the LGA (8/19), RIPA (10/19), LIPA (4/19), and RITA (3/19) was observed on post-ET CTA. The incidence of hepatic adverse events was significant in the group with both HAO and portal vein stenosis (p

Abstract Fluorescence‐guided surgery (FGS) aids surgeons with real‐time visualization of small cancer foci and borders, which improves surgical and prognostic efficacy of cancer. Despite the steady advances in imaging devices, there is a scarcity of fluorophores available to achieve optimal FGS. Here, 1) a pH‐sensitive near‐infrared fluorophore that exhibits rapid signal changes in acidic tumor microenvironments (TME) caused by the attenuation of intramolecular quenching, 2) the inherent targeting for cancer based on chemical structure (structure inherent targeting, SIT), and 3) mitochondrial and lysosomal retention are reported. After topical application of PH08 on peritoneal tumor regions in ovarian cancer‐bearing mice, a rapid fluorescence increase (< 10 min), and extended preservation of signals (> 4 h post‐topical application) are observed, which together allow for the visualization of submillimeter tumors with a high tumor‐to‐background ratio (TBR > 5.0). In addition, PH08 is preferentially transported to cancer cells via organic anion transporter peptides (OATPs) and colocalizes in the mitochondria and lysosomes due to the positive charges, enabling a long retention time during FGS. PH08 not only has a significant impact on surgical and diagnostic applications but also provides an effective and scalable strategy to design therapeutic agents for a wide array of cancers.

To evaluate the ability of double-echo steady-state (DESS) MRI to detect pars interarticularis fracture and bone marrow edema (BME) in spondylolysis, 500 lumber pars interarticularis from 50 consecutive patients (38 males and 12 females, mean age 14.2 ± 3.28 years) with spondylolysis who underwent both MRI and CT within 1 week were evaluated. All participants were young athletes who complained of lower back pain. Fractures were classified into four grades and CT was used as a reference; BME was evaluated in a binary manner and STIR was used as a reference. The diagnostic performance of fractures on DESS and T1WI, and BME on DESS was assessed by two radiologists independently. For fracture detection, DESS showed high diagnostic performance at a sensitivity of 94%, specificity of 99.5%, and accuracy of 98.8%, whereas T1WI showed lower sensitivity (70.1%). Fracture grading performed by DESS showed excellent agreement with CT grading (Kappa = 0.9). For BME, the sensitivity, specificity, and accuracy of DESS were 96.5%, 100%, and 99.6%, respectively. The inter-rater agreement of DESS for fracture and BME was 0.8 and 0.85, respectively. However, the inter-rater agreement for fracture on T1WI was 0.52. DESS had high diagnostic performance for fracture and BME in pars interarticularis. In conclusion, DESS had potential to detect all critical imaging findings in spondylolysis and may replace the role of CT.

Abstract Background Existing ultrashort echo time magnetic resonance imaging (UTE MRI) methods require prohibitively long acquisition times (~ 20–40 min) to quantitatively assess the clinically relevant fast decay T2* component in ligaments and tendons. The purpose of this study was to evaluate the feasibility and clinical translatability of a novel abbreviated quantitative UTE MRI paradigm for monitoring graft remodeling after anterior cruciate ligament (ACL) reconstruction. Methods Eight patients who had Graftlink™ hamstring autograft reconstruction were recruited for this prospective study. A 3D double-echo UTE sequence at 3.0 Tesla was performed at 3- and 6-months post-surgery. An abbreviated UTE MRI paradigm was established based on numerical simulations and in vivo validation from healthy knees. This proposed approach was used to assess the T2* for fast decay component ( T2s∗ $$ {T}_{2s}^{\ast } $$) and bound water signal fraction (f bw ) of ACL graft in regions of interest drawn by a radiologist. Results Compared to the conventional bi-exponential model, the abbreviated UTE MRI paradigm achieved low relative estimation bias for T2s∗ $$ {T}_{2s}^{\ast } $$ and f bw over a range of clinically relevant values for ACL grafts. A decrease in T2s∗ $$ {T}_{2s}^{\ast } $$ of the intra-articular graft was observed in 7 of the 8 ACL reconstruction patients from 3- to 6-months (− 0.11 ± 0.16 ms, P = 0.10). Increases in T2s∗ $$ {T}_{2s}^{\ast } $$ and f bw from 3- to 6-months were observed in the tibial intra-bone graft ( ΔT2s∗ $$ {\varDelta T}_{2s}^{\ast } $$: 0.19 ± 0.18 ms, P

Vital-sign estimation using ultra-wideband (UWB) radar is preferable because it is contactless and less privacy-invasive. Recently, many approaches have been proposed for estimating heart rate from UWB radar data. However, their performance is still not reliable enough for practical applications. To improve the accuracy, this study employs convolutional neural networks to learn the special patterns of the heartbeats. In the proposed system, skin displacements of the target person are measured using UWB radar, and the radar signal is converted to a two-dimensional matrix, which is used as the input of the designed neural networks. Meanwhile, two triangular waves corresponding to the peaks and valleys in an electrocardiogram are adopted as the output of the networks. The proposed system then identifies each individual and estimates the heart rate automatically based on the already trained neural networks. The estimation error of the interbeat interval computed using our approach was reduced to 4.5 ms in the best case; and 48.5 ms in the worst case. Experiment results show that the proposed approach significantly outperforms a conventional method. The proposed machine learning approach achieves both personal identification and heart rate estimation simultaneously using UWB radar data for the first time. Moreover, this study found that using the respiration and heartbeat components together may enhance the accuracy of heart rate estimation, which is counter-intuitive, because the respiration is usually believed to interfere with the heartbeat.

Objective: This study aimed to identify the detailed location of inflammatory lesions and its frequency of hand PsA on DECT Iodine Map with referring the cadaveric specimen. Materials and methods: Thirty-eight anatomical landmarks were selected as a potential inflammatory sites in the thumb and middle finger. We included 22 symptomatic PsA patients who underwent contrast enhanced DECT of the hand. MR images and macroscopic specimens of thumb and middle finger were prepared from a cadaver. Two musculoskeletal radiologists evaluated DECT with referring the cadaveric images to determine the precise location of inflammatory sites and its frequency. Results: The frequently observed inflammation sites of active PsA patients were either classical or functional entheses, and coincide with the well-known hypothesis that primary inflammatory sites of PsA are enthesis. We have noticed that there was remarkable enhancement around DIP joints (13.6 %–45.5 %). Conclusion: DECT could assess the detailed anatomical sites of the inflammatory lesion in hand psoriatic arthritis, which coincided with enthesis.

Abstract Background Ovarian serous borderline tumor/atypical proliferative serous tumor (SBT/APST) is characterized by presenting at an early stage and much longer survival than high-grade serous carcinoma. Given that the prognosis of ovarian SBT/APST with no invasive features is excellent, remote relapse after surgery can pose a diagnostic pitfall. Bone metastasis as transformed low-grade carcinoma is an extremely rare initial presentation of recurrence in patients whose primary tumor was confined to the ovaries. Case presentation A 55-year-old Japanese woman who had undergone surgery for a right ovarian tumor 13 years previously presented with right-lateral chest pain and neurologic abnormalities in the lower limbs. Computed tomography (CT) scan and magnetic resonance imaging revealed an irregular mass in the right arch of the 12th thoracic vertebra, extending through the intervertebral foramen and into surrounding soft tissue, the maximum diameter of the whole mass being 78 mm. Pathological examination of a CT-guided needle biopsy of the paraspinal lesion demonstrated papillary cell clusters with blunt nuclear atypia and psammomatous calcification that were positive for PAX8, estrogen receptor, and WT1, but negative for thyroglobulin on immunohistochemical testing, and of a P53 non-mutational pattern. On clinicopathologic review, the previous 13- × 11- × 9-cm ovarian tumor was an intracystic and exophytic papillary growth without surface involvement; it had ruptured intraoperatively. Microscopically there was serous epithelium with minimal cytologic atypia proliferating in hierarchical branches with no invasive foci or micropapillary components. The tumor was confined to the right ovary with no peritoneal implants. Neither primary nor metastatic tumor harbored KRAS/BRAF mutations according to polymerase chain reaction using formalin-fixed paraffin-embedded tissues. We concluded that, after a 13-year disease-free interval, the paraspinal lesion was bone metastasis of low-grade carcinoma originating from the ovarian SBT/APST. The patient received radiotherapy for the paraspinal lesion followed by administration of paclitaxel and carboplatin plus bevacizumab and remains alive 168 months after the initial surgery. Conclusions Pathologists and radiologists should not exclude late recurrence of ovarian SBT/APST when bone metastases are suspected, even when neither peritoneal nor lymph node involvement are detected. Long-term surveillance of women with ovarian serous tumors with no invasive features is recommended.

Abstract Background The combination of budesonide + formoterol (BFC) offers the advantages of dose adjustment in a single inhaler according to asthma symptoms. We analyzed the relationship between asthma symptoms in terms of peak expiratory flow (PEF) and dose adjustment by the patient. Methods Twenty-eight patients with asthma who used BFC for alleviation of their symptoms (12 men, 16 women; 60 years old) were instructed that the inhaled BFC dose could be increased to a maximum of 8 inhalations per day according to symptom severity. Patients measured and recorded PEF every morning and evening in their asthma diary along with their symptoms and the dose of drugs taken. Results Sixteen of the 28 patients increased their dose for asthma symptoms. The time to recovery from the asthma symptoms was significantly shorter when cough was the only symptom present compared with dyspnea or wheeze (1.4 vs. 5.3 or 6.6 days, p

Most gallbladder carcinomas are adenocarcinomas, of which mucinous carcinoma (MC) is a rare pathologic subtype. Signet ring cells are seldom found in MCs. We report an extremely rare case of gallbladder MC with signet ring cells. This is the first radiological case report about this rare type of histologic entity with detailed discussion of imaging findings in the English literature. In addition to the features of MC, linitis plastica-like invasion, which is the key feature of signet ring cells, was confirmed by both imaging and histopathologic analysis. Furthermore, radiologists should know how the imaging findings of MC differ from those of other major subtypes of adenocarcinoma, as there is a risk of delays in diagnosis and underestimation of tumor spread.

Abstract Background Intelectin-1 (ITLN-1) is secreted by intestinal goblet cells and detectable in blood. Its expression is increased in IL-13-overexpressing mouse airways. However, its expression and function in human airways is poorly understood. Methods Distal and proximal bronchial epithelial cells (BECs) were isolated from bronchoscopic brushings of disease control (D-CON), COPD, inhaled corticosteroid-treated asthma (ST-Asthma) and inhaled corticosteroid-naïve asthma (SN-Asthma) patients. ITLN-1 mRNA expression in freshly isolated BECs, primary cultured BECs with or without IL-13 and inhibition effects of mometasone furoate (MF) were investigated by quantitative real-time PCR (qPCR). Correlations between ITLN-1 mRNA and Type-2 related parameters (e.g. FeNO, IgE, iNOS, CCL26, periostin and DPP4 mRNA) were analyzed. ITLN-1 protein distribution in asthmatic airway tissue was assessed by immunohistochemistry. Bronchial alveolar lavage (BAL) and serum ITLN-1 protein were measured by ELISA. The effect of recombinant human (rh) ITLN-1 on stimulated production of CXCL10 and phospho(p)-STAT1 expression examined in lung fibroblasts. Results ITLN-1 mRNA was expressed in freshly isolated BECs and was correlated with Type-2 related parameters. ITLN-1 protein was increased in goblet cells in SN-Asthmatics and increased in SN-Asthmatic BAL fluid. There were no any differences in serum ITLN-1 concentration between ST and SN-Asthma. IL-13 enhanced ITLN-1 expression and inhibited by MF from BECs in vitro, while rhITLN-1 inhibited CXCL10 production and p-STAT1 expression in HFL-1 cells. Conclusion ITLN-1 is induced by IL-13 and expressed mainly in goblet cells in untreated asthma where its levels correlate with known Type-2 related parameters. Further, ITLN-1 inhibits Type-1 chemokine expression.

Abstract Magnetic resonance (MR) imaging plays an important role in the evaluation of bacterial and tuberculous spondylodiscitis and associated complications. Owing to its high sensitivity and specificity, it is a powerful diagnostic tool in the early diagnosis of ongoing infections, and thus provides help in prompt initiation of appropriate, therapy which may be medical or surgical, by defining the extent of involvement and detection of complications such as epidural and paraspinal abscesses. More specifically, MR imaging helps in differentiating bacterial from tuberculous infections and enables follow up of progression or resolution after appropriate treatment. However, other non-infectious pathology can demonstrate similar MR imaging appearances and one should be aware of these potential mimickers when interpreting MR images. Radiologists and other clinicians need to be aware of these potential mimics, which include such pathologies as Modic type I degenerative changes, trauma, metastatic disease and amyloidosis. In this pictorial review, we will describe and illustrate imaging findings of bacterial and tuberculous spondylodiscitis, their complications and non-infectious pathologies that mimic these spinal infections.

Background: Bronchial asthma is a common but important chronic disease in children in all over the world. To take measures against prevalence of childhood asthma, many researchers have surveyed the actual statuses of childhood asthma in developed countries, but in most Asia–Pacific developing countries including Mongolia such surveys have never been sufficiently conducted until now. We have thought that this survey, though performed in 2009, will give important and meaningful information even now in taking measures to prevent prevailing bronchial asthma in children in Mongolia or the countries under similar statuses. Methods: The asthma prevalence and patient background information in Mongolian children aged 6–7 living in Ulaanbaatar were examined using a written questionnaire modified for their parents from that prepared by the International Study of Asthma and Allergies in Childhood (ISAAC). Results: The estimated prevalence of asthma in Mongolian children was 20.9%. The following 3 risk factors were found to be related to asthma: (1) having allergic rhinitis symptoms, (2) mothers' smoking, and (3) history of severe respiratory infection before 1-year-old. Conclusions: The asthma prevalence in Mongolian children was higher than that in the world and Asia–Pacific countries reported by ISAAC. The higher prevalence was probably attributable to households' (especially mothers) smoking in draft-free houses designed for the cold area and severe air-pollution due to rapid industrialization and urbanization in Mongolia. Smoking prohibition in the mother (including family members) and a reduction of exposure to air pollutants are urgently needed to prevent developing childhood asthma.

We constructed ZnO/PbS quantum dot (QD) heterojunction solar cells using liquid-phase ligand exchange methods. Colloidal QD solutions deposited on ZnO-dense layers were treated at different temperatures to systematically study how thermal annealing temperature affected carrier transport properties. The surface of the layers became dense and smooth as the temperature approached approximately 80 °C. The morphology of layers became rough for higher temperatures, causing large grain-forming PbS QD aggregation. The number of defect states in the layers indicated a valley-shaped profile with a minimum of 80 °C. This temperature dependence was closely related to the amount of residual n-butylamine complexes in the PbS QD layers and the active layer morphology. The resulting carrier diffusion length obtained on the active layers treated at 80 °C reached approximately 430 nm. The solar cells with a 430-nm-thick active layer produced a power conversion efficiency (PCE) of 11.3%. An even higher PCE is expected in solar cells fabricated under optimal annealing conditions.

In order to realize deep laser welding, conceptual application of a supersonic jet as an aerodynamic window was investigated. Detailed characteristics of the supersonic jet as the aerodynamic window were studied experimentally. Flow field of the supersonic jet was examined based on the schlieren flow visualization technique. As compared to a free-vortex flow design applied to the aerodynamic window nozzle, in the case of supersonic jet, oblique shock waves were captured both at the nozzle exit edge and the shear layer on the aerodynamic window. The velocity field under the condition that the shock - expansion wave was formed in the aerodynamic window was measured by the PIV (Particle Image Velocimetry) system (Koncerto II, Seika Digital Image Corp.) . Both the vorticity magnitude and angular momentum were analyzed. Level of the vorticity magnitude in the core region of the supersonic jet was smaller by one-order than that in the shear layer in the region corresponding to the passage of laser-light (θ = 30 to 40° and r = 23.8 to 27.1 mm). The radial and circumferential velocity product in this region was similar to that observed under the free-vortex condition. In addition to the measurement mentioned above, pressure behavior was investigated using a multi-pressure measuring system (Scanivalve Corp. ZOC33). When the reservoir pressure was set at 800 kPa and diffuser width as 30.0mm, cavity pressure was reduced to 10.0 kPa. Under this reduced pressure environment, penetration depth increased by 2.6 times compared to penetration depth under atmospheric pressure environment. The effectiveness of the supersonic free-vortex aerodynamic window system tested in the high power laser welding manufacturing has been proven by the present study.

Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naïve CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in naturally occurring memory phenotype CD4+ T (MPT) cells and their derived TH2 (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient mice, and reporter mice for conserved noncoding sequence 2 (CNS2) 3′ distal enhancer region were used to elucidate Bcl6 function in MPT cells. The molecular mechanisms of Bcl6-mediated TH2 cytokine gene regulation were elucidated using cellular and molecular approaches. Bcl6 function in MPT cells was determined using adoptive transfer to naïve mice, which were assessed for allergic airway inflammation. Bcl6 suppressed IL-4 production in MPT and MPTH2 cells by suppressing CNS2 enhancer activity. Bcl6 downregulated Il4 expression in MPTH2 cells, but not MPT cells, by suppressing hcIE activity. The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies.

Background:: Forestry and field workers who work outdoors are at high risk for Hymenoptera stings and may develop occupation-related allergies from being stung. However, clinical and immunological surveys of Hymenoptera stings in the occupational setting have rarely been reported. We surveyed the natural history of Hymenoptera stings in Japanese forestry workers (FWs) and electrical facility field workers (EFFWs), and we assessed the utility of measuring specific (s)IgE Ab to Hymenptera venom. Methods:: Questionnaires on hornet and paper wasp stings were completed by 999 FWs, 354 EFFWs, and 365 office workers as controls between July and November 2009. Sera from these participants were tested for sIgE Ab levels to Hymenptera venom with a CAP system using a fluoroenzyme immunoassay. Results:: Of the participants who had experienced Hymenoptera stings, 914 (91.5%) were FWs, 293 (82.8%) were EFFWs, and 295 (80.8%) were controls. Of the participants who had experienced systemic reactions, 210 (21.0%) were FWs, 51 (14.4%) were EFFWs, and 39 (10.7%) were controls. sIgE Ab in response to hornet and wasp venom was positive (≥ class 2) in 42.4% and 41.4% of FWs, 30.1% and 31.4% of EFFWs, and 15.1% and 18.1% of controls, respectively. The likelihood of being sIgE-positive to wasp and hornet venom was significantly higher in FWs and EFFWs than in controls (P < 0.05). Conclusions:: 21% of FWs and 14% of EFFWs had experienced systemic reactions to Hymenoptera stings with a higher frequency compared with office workers in the same area. 40% of FWs and 30% of EFFWs had sera that were sIgE positive to Hymenoptera venom.

Two Prins reactions were investigated by the use of DFT calculations. A model composed of R–CH=CH2 + H3O+(H2O)13 + (H2C=O)2, R = Me and Ph, was adopted to trace reaction paths. For both alkenes, the concerted path forming 1,3-diols was obtained as the rate determining step (TS1). TS stands for a transition state. From the 1,3-diol, a bimolecular elimination (TS2) leads to the allylic alcohol as the first channel. In the second channel, the 1,3-diol was converted via TS3 into an unprecedented hemiacetal intermediate, HO–CH2–O–CH(R)–CH2–CH2–OH. This intermediate undergoes ring closure (TS4), affording the 1,3-dioxane product. The intermediate is of almost the same stability as the product, and two species were suggested to be in a state of equilibrium. While the geometry of TS1 appears to be forwarded to that of a carbocation intermediate, the cation disappeared through the enlargement of the water cluster. Dynamical calculations of a classical trajectory using the atom-centered density matrix propagation molecular dynamics model on the four TSs were carried out, and results of IRC calculations were confirmed by them.

Spray coating technique has been established as a promising substitute for the traditional coating methods in the fabrication of organic devices in many reports recently. Control of film morphology at the microscopic scale is critical if spray-coated devices are to achieve high performance. Here we investigate electrospray deposition protocols for the fabrication of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) thin films with a single additive system under ambient conditions at room temperature. Critical deposition parameters including solution composition, applied voltage, and relative humidity are discussed systematically. Optimized process for preparing homogenous PEDOT:PSS thin films is applied to all-electrospray-coated organic photovoltaic cells and contributes to a power conversion efficiency comparable to that of the corresponding all-spin-coated device.

A 56-year-old woman was referred to our hospital because of dyspnea, wheezing, and a productive cough. Eight years before presentation, bronchial asthma was diagnosed and the patient received inhaled corticosteroids plus antiasthmatic agents (a long-acting inhaled p2-agonist, leukotriene modifiers, and theophylline). Chest radiography showed small diffuse nodular shadows, and a computed tomographic scan showed thickening of the bronchi and bronchioles, with diffuse centrilobular nodules in both lung fields. A blood test and microscopic examination of the bronchoalveolar fluid revealed marked eosinophilia. Transbronchial lung biopsy and transbronchial biopsy showed eosinophilic bronchitis and bronchiolitis. After treatment with oral prednisolone (40 mg daily) and inhaled corticosteroids, the symptoms, blood eosinophilia, and radiographic findings improved. Recently, several similar cases of eosinophilic bronchiolitis have been reported. Studies of further cases and elucidation of the pathophysiology of eosinophilic bronchiolitis are necessary to establish a concept for this disease and to determine whether it should be classified as a subtype of bronchial asthma or as a distinct entity.

Background: Recent studies have suggested that allergic rhinitis is closely related to bronchial asthma, reflecting the "one airway-one disease" hypothesis. It is unclear if the effects of pranlukast, a leukotriene-receptor antagonist, are consistent with this hypothesis. Objective: The goal of the study was to determine if pranlukast has effects on the upper and lower airways through a comparison of the effects of fexofenadine and pranlukast on airway hyperresponsiveness in non-asthmatic patients with cedar pollinosis before the Japanese cedar pollen season and during the peak pollen season. Methods: Patients received fexofenadine hydrochloride plus oral mequitazine (fexofenadine group) or pranlukast hydrate plus oral mequitazine (pranlukast group) as an initial treatment. Subsequent changes in airway responsiveness to acetylcholine were measured. Results: Among patients in whom coughing developed during the peak pollen season, airway responsiveness significantly increased in the fexofenadine group. In the pranlukast group, airway responsiveness did not increase significantly, regardless of the presence or absence of coughing. Conclusions: The results indicate that pranlukast hydrate inhibits airway hyperresponsiveness in non-asthmatic patients with Japanese cedar pollinosis. In turn, this suggests that cysteinyl leukotrienes have a role in increased airway responsiveness.

Various molecules participate in different phases of allergic reactions. This means that many genes are encoding molecules related to allergic reactions, such as cytokines, chemokines, and their receptors as effector molecules. The transcriptional repressor BCL6 has emerged as a multifunctional regulator of lymphocyte differentiation and immune responses. BCL6-deficient (BCL-/-) mice display T helper type 2 (Th2)-type inflammation, which is caused by abnormality of both lymphoid cells and nonlymphoid cells. Thus, BCL6 apparently contributes to negative regulation of various central molecules such as cytokines, in particular Th2 cytokines, CC chemokines, and immunoglobulin E in allergic diseases. Therefore, BCL6 may be a molecular target for Th2-type allergic diseases. Keywords: allergy, BCL6, cytokine, chemokine, lgE, Th2, transcriptional repressor

Background: Injectable methylxanthines are useful drugs in the treatment of asthma. The Asthma Prevention and Management Guidelines (JGL) that are followed in Japan recommend the use of sustained-release theophylline to control the disease and use of injectable methylxanthines to alleviate symptoms. In contrast, the guidelines followed in the west do not promote theophylline use due to safety concerns, and the use of injectable methylxanthines in particular are not recommended. We thus conducted a study on adult patients with bronchial asthma or chronic obstructive pulmonary disease treated with theophylline and injectable methylxanthines in Japan in order to assess the safety of these drugs. Methods: 876 patients were surveyed at 55 medical institutions by the Committee on the Safety of Sustained-Release Theophylline and Injectable Methylxanthines (CST) of the Committee for Asthma Prevention and Management Guidelines of the Japanese Society of Allergology (JSA). 682 of the patients were evaluated for safety. Results: Adverse reactions including facial flushing, palpitations, headache, tinnitus, diaphoresis, nausea, vomiting and tachycardia were reported by only 2 (0.29%) of the 682 patients, but none of these were serious. Conclusions: The results confirm that injectable methylxanthines are safe, when used in accordance with the JGL.

Background: Theophylline is a useful drug for the treatment of asthma. The Asthma Prevention and Management Guidelines (JGL) recommend use of sustained-release theophylline products as controllers and of injectable aminophylline products as relievers. The Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention, the NHLB/WHP Workshop Report 1995 (GINA, 1995) and guidelines in Western countries recommend sustained-release theophylline, but not as positively as in the JGL. The aim of this survey was to determine the occurrence of serious adverse reactions. Methods: The survey was conducted in 66 institutions staffed by physicians certified by the Japanese Society of Allergology (JSA). The target diseases were asthma and COPD including chronic bronchitis and pulmonary emphysema, which are indications for use of sustained-release theophylline products in Japan. Results: 3,921 patients were included in the safety evaluation. No serious adverse reactions were observed among the patients in this survey, although 54 patients (1.38%) exhibited non-serious adverse reactions. The incidence of adverse reactions was found to be high in patients who had begun use of sustained-release theophylline products at the time of registration in this survey, and in patients who were concomitantly taking macrolide antibiotics. Conclusions: The present survey demonstrates that sustained-release theophylline is safe, as long as used appropriately, although adverse reactions tend to develop early after initiation of administration.

A molybdenum trioxide thin film with smooth surface and uniform thickness was successfully achieved by an electrospray deposition method using an aqueous solution with a drastically low concentration of 0.05 wt%. Previous papers demonstrated that an additive solvent technique is useful for depositing the thin film by the electrospray deposition, and the high vapor pressure and a low surface tension of an additive solvent were found to be important factors. As a result, the smooth molybdenum trioxide thin film was obtained when the acetonitrile was used as the additive solvent. Furthermore, the vapor pressure of acetone is much higher than that of aqueous solution, and this indicates that the acetone is easily evaporated after spraying from the glass capillary. By optimizing a concentration of acetone in the molybdenum aqueous solution, a minimum root mean square roughness of the MoO3 thin film became 3.7 nm. In addition, an organic photovoltaic cell was also demonstrated using the molybdenum trioxide as a hole transport layer. Highest photoconversion efficiency was 1.72%, a value comparable to that using conventional thermal evaporation process even though the aqueous solution was used for the solution process. The photovonversion efficiency was not an optimized value, and the higher value can be achieved by optimizing the coating condition of the active layer.

To analyze the prevalence and severity of asthma, rhinitis and eczema in children living in different countries, the International Study of Asthma and Allergies in Childhood (ISAAC) was developed. The ISAAC Phase One study evaluated approximately 720 000 children in 56 countries, including Japan. In late 1995 and early 1996, we administered the ISAAC questionnaire to 4466 schoolchildren aged 13–14 years of age in 24 schools in Utsunomiya City and Tochigi City (both in Tochigi Prefecture, Japan). With regard to asthma, the reported prevalence of wheezing in the preceding 12 months was 8.4%, of frequent wheezing attacks 0.6% and of wheezing with sleep disturbance 0.5%. The prevalence in the preceding 12 months of rhinitis was 42.1% and of rhinoconjunctivitis was 21.5%. Nasal symptoms were most frequent in April (19.9%) and least frequent in July (5.6%). The prevalence of atopic eczema in the prior 12 months was 9.6% and atopic eczema with sleep disturbance was 0.6%. All prevalence values were slightly increased in Utsunomiya City, the largest city in Tochigi Prefecture, in comparison with Tochigi City. In conclusion, in Japanese cities, 33.3% of children had some allergic symptoms and 2.4% of children reported severe allergic symptoms.

ABSTRACT Lipomannan (LM) and lipoarabinomannan (LAM) are mycobacterial glycolipids containing a long mannose polymer. While they are implicated in immune modulations, the significance of LM and LAM as structural components of the mycobacterial cell wall remains unknown. We have previously reported that a branch-forming mannosyltransferase plays a critical role in controlling the sizes of LM and LAM and that deletion or overexpression of this enzyme results in gross changes in LM/LAM structures. Here, we show that such changes in LM/LAM structures have a significant impact on the cell wall integrity of mycobacteria. In Mycobacterium smegmatis, structural defects in LM and LAM resulted in loss of acid-fast staining, increased sensitivity to β-lactam antibiotics, and faster killing by THP-1 macrophages. Furthermore, equivalent Mycobacterium tuberculosis mutants became more sensitive to β-lactams, and one mutant showed attenuated virulence in mice. Our results revealed previously unknown structural roles for LM and LAM and further demonstrated that they are important for the pathogenesis of tuberculosis. IMPORTANCE Tuberculosis (TB) is a global burden, affecting millions of people worldwide. Mycobacterium tuberculosis is a causative agent of TB, and understanding the biology of M. tuberculosis is essential for tackling this devastating disease. The cell wall of M. tuberculosis is highly impermeable and plays a protective role in establishing infection. Among the cell wall components, LM and LAM are major glycolipids found in all Mycobacterium species, show various immunomodulatory activities, and have been thought to play roles in TB pathogenesis. However, the roles of LM and LAM as integral parts of the cell wall structure have not been elucidated. Here we show that LM and LAM play critical roles in the integrity of mycobacterial cell wall and the pathogenesis of TB. These findings will now allow us to seek the possibility that the LM/LAM biosynthetic pathway is a chemotherapeutic target.

We have identified coal tar pitch, a very cheap organic material made from coal during the iron-making process, as a source from which could be obtained emissive molecules for organic light-emitting diodes. Coal tar pitch was separated by simple dissolution in organic solvent, and subsequent separation by preparative thin-layer chromatography was used to obtain emissive organic molecules. The retardation factor of preparative thin-layer chromatography played a major role in deciding the emission characteristics of the solution as photoluminescence spectra and emission-excitation matrix spectra could be controlled by modifying the solution preparation method. In addition, the device characteristics could be improved by modifying the solution preparation method. Two rounds of preparative thin-layer chromatography separation could improve the luminance of organic light-emitting diodes with coal tar pitch, indicating that less polar components are favorable for enhancing the luminance and device performance. By appropriate choice of the solvent, the photoluminescence peak wavelength of separated coal tar pitch could be shifted from 429 nm (cyclohexane) to 550 nm (chloroform), and consequently, the optical properties of the coal tar pitch solution could be easily tuned. Hence, the use of such multicomponent materials is advantageous for fine-tuning the net properties at a low cost. Furthermore, an indium tin oxide/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)/coal tar pitch/LiF/Al system, in which the emissive layer was formed by spin-coating a tetrahydrofuran solution of coal tar pitch on the substrate, showed a luminance of 176 cd/m(2). In addition, the emission spectrum of coal tar pitch was narrowed after the preparative thin-layer chromatography process by removing the excess emissive molecules.

Ovarian serous carcinoma is a gynecological malignancy associated with a high mortality rate, which is commonly diagnosed in the first instance at a late stage and has a propensity to develop resistance to platinum-based chemotherapy. Identifying reliable biomarkers for platinum sensitivity is critical for improving patient outcomes. The present retrospective study included 64 patients with high-grade serous ovarian carcinoma (Federation of Gynecology and Obstetrics stages III or IV). Patients were classified as platinum-sensitive (no relapse within 6 months of the last platinum administration) or platinum-resistant (relapse within 6 months). Immunohistochemical analysis was performed to evaluate Fyn expression in tumor tissues, and Fyn knockdown experiments were performed using the OVSAHO ovarian cancer cell line to assess carboplatin sensitivity. Fyn expression was significantly higher in platinum-resistant patients compared with in platinum-sensitive patients (P<0.01). A weighted Fyn expression score was developed and a cutoff score of 6 was determined to predict platinum sensitivity with a specificity of 65.5% and a sensitivity of 62.9%. Patients with low Fyn expression (score ≤6) exhibited higher platinum sensitivity and longer overall survival (P<0.05). Multivariate analysis identified Fyn expression and postoperative residual tumor size as independent predictors of platinum sensitivity (P=0.033 and P=0.023, respectively). In vitro, Fyn knockdown significantly increased carboplatin sensitivity in ovarian cancer cells (P<0.05). Fyn, a member of the Src family of kinases, serves a crucial role in various cellular functions and has been implicated in chemotherapy resistance. The results demonstrated a notable association between Fyn expression and platinum sensitivity in ovarian serous carcinoma. The findings suggested that Fyn may serve as a predictive biomarker for response to platinum-based chemotherapy, offering the potential for more personalized treatment strategies. To the best of our knowledge, the present study is the first to establish an association between Fyn expression and platinum sensitivity in advanced ovarian serous carcinoma. Prospective studies with larger, multi-center cohorts and comprehensive biomarker analyses are recommended to validate and extend these results, ultimately improving therapeutic strategies and patient prognosis. [ABSTRACT FROM AUTHOR]