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We investigated whether magnetic resonance imaging can visualize the distribution in the vitreous cavity via eye drops of ophthalmic solutions, gadolinium-based contrast agent, and 17 O-water, and to clarify the usefulness of ultra-heavily T2-weighted sequences in the research of intraocular distribution. Five different solutions (V-ROHTO, TRAVATANZ, gadobutrol, H 2 17 O, and saline) were administered to excised pig eye specimens. The samples were scanned using T1 mapping, T2 mapping, 3D T2-weighted (echo times (TE): 500, 3200, and 4500 ms), a half-Fourier single-shot turbo-spin echo sequence (HASTE; TE: 440 and 3000 ms), and 3D-real inversion-recovery before eye drops administration. Subsequently, we used a plastic dropper to drop a 0.5 mL solution each, and images were obtained up to 26 h later. Temporal changes in the T1 and T2 values of the anterior chamber and vitreous cavity were compared. The other sequences were evaluated by determining temporal signal changes as signal intensity ratio (SIR) compared to "No drop." The T1 and T2 values of samples treated with gadobutrol and H 2 17 O decreased over time. The SIR of samples treated with gadobutrol and H 2 17 O showed remarkable changes in the 3D T2-weighted images, whereas no remarkable temporal changes were observed in the other solutions. Longer TEs resulted in remarkable changes. We demonstrated that visualization of distribution in the vitreous cavity via eye drops could be achieved with excised pig eyes using gadobutrol and H 2 17 O, but not with ophthalmic solutions. Ultra-heavily T2-weighted sequences may be promising for the early and highly sensitive visualization of the intraocular distribution of eye drops., (© 2024. The Author(s).)

Achaete-scute family bHLH transcription factor 2 (ASCL2) is highly expressed in hepatoblastoma (HB) tissues, but its role remains unclear. Thus, biological changes in the HB cell line HepG2 in response to induced ASCL2 expression were assessed. ASCL2 expression was induced in HepG2 cells using the Tet-On 3G system, which includes doxycycline. Cell viability, proliferation activity, mobility, and stemness were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation, migration, invasion, and sphere-formation assays. Quantitative reverse-transcription polymerase chain reaction was used to assess the expression of markers for proliferation (CCND1 and MYC), epithelial-mesenchymal transition (EMT; SNAI1, TWIST1, and ZEB1), mesenchymal-epithelial transition (CDH1), and stemness (KLF4, POU5F1, and SOX9). Compared with the non-induced HepG2 cells, cells with induced ASCL2 expression showed significant increases in viability, colony number, migration area (%), and sphere number on days 7, 14, 8, and 7, respectively, and invasion area (%) after 90 h. Furthermore, induction of ASCL2 expression significantly upregulated CCND1, MYC, POU5F1, SOX9, and KLF4 expression on days 2, 2, 3, 3, and 5, respectively, and increased the ratios of SNAI1, TWIST1, and ZEB1 to CDH1 on day 5. ASCL2 promoted the formation of malignant phenotypes in HepG2 cells, which may be correlated with the upregulation of the Wnt signaling pathway-, EMT-, and stemness-related genes. ASCL2 activation may therefore be involved in the progression of HB., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients., (© 2024. The Author(s).)

Background: Currently, the standard curative treatment for ventricular tachycardia (VT) and ventricular fibrillation (VF) is radiofrequency catheter ablation. However, when the VT circuit is deep in the myocardium, the catheter may not be delivered, and a new, minimally invasive treatment using different energies is desired., Methods: This is a protocol paper for a feasibility study designed to provide stereotactic radiotherapy for refractory VT not cured by catheter ablation after at least one catheter ablation. The primary end point is to evaluate the short-term safety of this treatment and the secondary endpoint is to evaluate its efficacy as assessed by the reduction in VT episode. Cyberknife M6 radiosurgery system will be used for treatment, and the prescribed dose to the target will be 25Gy in one fraction. The study will be conducted on three patients., Conclusion: Since catheter ablation is the only treatment option for VT that is covered by insurance in Japan, there is currently no other treatment for VT/VF that cannot be cured by catheter ablation. We hope that this feasibility study will provide hope for patients who are currently under the stress of ICD activation., Trial Registration: The study has been registered in the Japan Registry of Clinical Trials (jRCTs042230030)., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Kawamura M et al.)

This study presents two cases of tumors in contact with the inferior vena cava during radiotherapy, and introduces a clinically useful technique for identifying tumor boundaries adjacent to blood vessels by adjusting the position of the field-of-view (FOV) to enhance the inflow effect in magnetic resonance imaging. We named this technique "Shifting-FOV." This method consists of three steps: (1) remove the upper and lower saturation pulses outside the FOV, (2) align the FOV to position the lower edge of the imaging slab as close to the tumor as possible, and (3) manually adjust the table position to locate the tumor at the center of the magnetic field. The proposed method allowed for accurate identification of the tumor/vessel boundaries in both cases. This is a useful technique that can be readily applied to other facilities. Furthermore, images obtained using this technique may enable accurate tumor contouring in radiotherapy treatment planning., (© 2023. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Bipolar disorder (BD) is a common psychiatric disorder, but its pathophysiology is not fully elucidated. The current study focused on its electrophysiological characteristics, especially power spectral density (PSD). Resting state with eyes opened magnetoencephalography data were collected from 21 patients with BD and 22 healthy controls. The whole brain's PSD was calculated from source reconstructed waveforms at each frequency band (delta: 1-3 Hz, theta: 4-7 Hz, alpha: 8-12 Hz, low beta: 13-19 Hz, high beta: 20-29 Hz, and gamma: 30-80 Hz). We compared PSD values on the marked vertices at each frequency band between healthy and patient groups using a Mann-Whitney rank test to examine the relationship between significantly different PSD and clinical measures. The PSD in patients with BD was significantly decreased in lower frequency bands, mainly in the default mode network (DMN) areas (bilateral medial prefrontal cortex, bilateral precuneus, left inferior parietal lobe, and right temporal cortex in the alpha band) and salience network areas (SAL; left anterior insula [AI] at the delta band, anterior cingulate cortex at the theta band, and right AI at the alpha band). No significant differences in PSD were observed at low beta and high beta. PSD was not correlated with age or other clinical scales. Altered PSDs of the DMN and SAL were observed in the delta, theta, and alpha bands. These alterations contribute to the vulnerability of BD through the disturbance of self-referential mental activity and switching between the default mode and frontoparietal networks., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: In order to prevent magnetic materials from being brought into the magnetic resonance imaging (MRI) examination room, many facilities have metal detectors, etc., but there are various types of equipment with different performance and characteristics. The purpose of this study was to evaluate each detector in actual clinical practice., Methods: At multiple facilities, gate-type magnetic detectors, pole-type magnetic detectors, handy-type magnetic detectors, and handy-type metal detectors were used to identify 9 types of objects that may be brought into the MRI examination room. We performed evaluation of detection distance measurement assuming actual operation., Results: The gate type was only able to detect objects with strong magnetism. With the pole type, the closer the measurement distance was to the pole, the more objects could be detected, and the lower the pole, the shorter the detection distance. With the handy type, there were many objects that could be detected when the device and the object were brought into close contact., Conclusion: The detectability of the instruments varied depending on the size and type of the object. It is important to understand the characteristics of each device and use it according to the purpose in carrying-in confirmation before the examination.

Prostatic urethra identification is crucial in prostate stereotactic body radiotherapy (SBRT) to reduce the risk of urinary toxicity. Although computed tomography (CT) with a catheter is commonly employed, it is invasive, and catheter placement may displace the urethral position, resulting in possible planning inaccuracies. However, magnetic resonance imaging (MRI) can overcome these weaknesses. Accurate urethral identification and minimal daily variation could ensure a highly accurate SBRT. In this study, we investigated the usefulness of a three-dimensional (3D) T2-weighted (T2W) sequence for urethral identification, and the interfractional motion of the prostatic urethra on CT with a catheter and MRI without a catheter for implementing noninvasive SBRT. Thirty-two patients were divided into three groups. The first group underwent MRI without a catheter to evaluate urethral identification by two-dimensional (2D)- and 3D-T2W sequences using mean slice-wise Hausdorff distance (MSHD) and Dice similarity coefficient (DSC) of the contouring by two operators and using visual assessment. The second group provided 3-day MRI data without a catheter using 3D-T2W, and the third provided 3-day CT data with a catheter to evaluate the interfractional motion using MSHD, DSC, and displacement distance (Dd). The MSHD and DSC for the interoperator variability in urethral identification and visual assessment were superior in 3D-T2W than in 2D-T2W. Regarding interfractional motion, the Dd value for prostatic urethra was smaller in MRI than in CT. These findings indicate that the 3D-T2W yielded adequate prostatic urethral identification, and catheter-free MRI resulted in less interfractional motion, suggesting that 3D-T2W MRI without a catheter is a feasible noninvasive approach to performing prostate SBRT., Competing Interests: The authors declare that they have no conflicts of interest.

Purpose: Due to technological advancements, surgical invasiveness has been reduced. However, cataract surgery has been implicated in causing postoperative inflammation, including dry eye syndrome. The innate immune system may be involved in postoperative inflammation, and complement activation could potentially play a crucial role in defense against pathogens, homeostasis, and wound healing. To investigate changes in the tear film complement activation products (CAPs) and ocular surface after vitrectomy combined with cataract surgery., Methods: Forty-three patients (23 women; median age, 69 years) were enrolled in this prospective study and underwent phacoemulsification and vitrectomy. We measured Schirmer's test (ST) and CAPs in the tears at baseline (the day before surgery), 4 days and 1 month after the surgery. Tears were collected in microtubes. The CAPs in the tear fluid were analyzed by cytometric bead array., Results: The median ST (8.5 mm) at baseline increased to 16 mm at 4 days ( P < 0.001) and 10 mm at 1 month (P = 0.44). The C3a levels (1202 pg/ml) at baseline increased to 2753 pg/ml at 4 days (P < 0.001), and 1763 pg/ml at 1 month (P = 0.049). The C4a levels (476 pg/ml) at baseline increased to 880 pg/ml at 4 days (P < 0.001), and 657 pg/ml at 1 month (P = 0.013). The C5a levels (22.6 pg/ml) at baseline increased to 470.9 pg/ml at 4 days (P < 0.001), and 38.3 pg/ml at 1 month (P = 0.0048). The surgical eyes were divided into the short ST group (≦ 10 mm, n = 22) and long ST group (> 10 mm, n = 21) based on the preoperative ST values. At 1 month postoperatively, the C3a levels were 2194 pg/ml in the preoperative short ST group and 1391 pg/ml in the long ST group, with significantly higher C3a concentrations in the short ST group (P < 0.001)., Conclusions: The CAPs levels in tears increased after vitrectomy combined with cataract surgery. A preoperative deficit in tear secretion might induce prolonged complement activation and delayed recovery of ocular surface parameters postoperatively., (© 2023. The Author(s).)

Purpose: To determine whether T2-contrast enhancement techniques can be used to diagnose endolymphatic hydrops, we compared fluid signal artifacts with and without T2-contrast enhancement techniques in 3D fluid-attenuated inversion recovery (3D-FLAIR)., Methods: We prepared a custom-made phantom consisting of eight tubes half-filled with saline. Images were obtained using four 3D-FLAIR: without T2-contrast enhancement (Normal), with non-selective T2-inversion recovery (T2-IR), and two with non-selective T2 preparation IR (T2-prep). Scans were performed with and without rice covering the phantom to simulate minimal and severe B0-inhomogeneity conditions. The average signal intensity (SI) values of eight saline tubes were compared between the four sequences and between each other. Comparisons were performed for all measurement slices and the central 10 slices. The images using T2-contrast enhancement technique were obtained from a volunteer and a patient suspected of Meniere's disease., Results: The Normal sequence SI for all slices was significantly lower than that for the other sequences, with smaller standard deviation (SD) and no outliers. Several outliers were detected in the other sequences. The SDs and outliers were larger without rice than with rice. When the central 10 slices with rice, the T2-IR had a significantly higher SI with more outliers compared with the Normal sequence. The T2-prep had no outliers and SIs that were comparable to those of the Normal sequence. However, without rice, the T2-IR and T2-prep sequences had significantly higher SIs with outliers and larger SDs compared to the Normal sequence. In the corresponding images, the Normal sequence achieved excellent fluid suppression, whereas the T2-IR and T2-prep sequences showed high-signal artifacts. Imperfect fluid suppressions were observed in the volunteer image and the endolymphatic hydrops on the post-gadolinium image differed in size and shape in the non-injected T2-IR in the patient image., Conclusion: T2-contrast enhancement techniques should be used with caution in 3D-FLAIR for diagnosing endolymphatic hydrops.

Purpose: We examined the effect of ranibizumab with or without laser photocoagulation on retinal sensitivity in eyes with branch retinal vein occlusion., Methods: Prospective randomized control study. Thirty patients with branch retinal vein occlusion received intravitreal injection of ranibizumab in a monthly pro re nata regimen. Fifteen patients received ranibizumab monotherapy alone (monotherapy group). The remaining 15 patients received rescue laser therapy at 3 or 9 months (combined group). The retinal sensitivity was measured at 32 points within central 8°, and the average of the main occlusion side among the 16 upper or 16 lower points was defined as the affected area sensitivity., Results: In comparing the monotherapy group and the combined group, the number of injections during the 12 months was 5.4 versus 4.9, the change in retinal thickness ( µ m) was -254 versus -197, the ETDRS letters of improvement was +18.3 versus +19.6, and the change in the affected area sensitivity (dB) was +7.1 versus +4.6. At 12 months, all these results were significantly improved compared with their respective baselines, but none of the differences between the two groups reached statistical significance., Conclusion: Retinal sensitivity at 12 months improved in both the monotherapy group and the combined group. The additional laser did not reduce the number of injections or further improve visual acuity nor did it affect retinal sensitivity.

The patient, a 56-year-old lady, also exhibited numerous lymphadenopathy, hepatosplenomegaly, hyperleukocytosis (167,200/µl, aberrant lymphocytes 91.5%), and fever. A lymph node biopsy revealed follicular lymphoma (FL), grade 1. Peripheral blood tumor cells did not express CD10, which was a distinctive characteristic of the lymph node specimen. To prevent tumor lysis syndrome (TLI), CHOP was delivered without an anti-CD20 antibody, but afterward, residual lymphoma cells were found in peripheral blood (>80%). As a result, obinutuzumab (Obi) was given on day 8 following the second round of CHOP, and the tumor cells in the peripheral blood vanished without any major side effects like TLI. She underwent six chemotherapy sessions before receiving maintenance therapy with Obi and achieving a full metabolic response. According to reports, leukemic FL exhibits negative CD10 expression in peripheral blood lymphoma cells, while leukemic mantle cell lymphoma also shows this trait. Therefore, it is important not to confuse the two types in diagnosis. Leukemic FL with significant leukocytosis is reportedly uncommon and has a bad prognosis. Our case indicates that CHOP with Obi would be a good alternative for cases like yours, however, there have been a few cases recorded. Further case accumulation or investigation is warranted.

We evaluated the inner ear distribution of 17 O-labeled saline administered to the human tympanic cavity. Magnetic resonance imaging was performed after intratympanic administration in five healthy volunteers and one patient with cochlear endolymphatic hydrops. In all volunteers, 17 O-labeled water permeated the cochlear basal turn and vestibule at 30 min and disappeared gradually within 2-4 h. All participants experienced positional vertigo lasting a few hours to a few days. Visualization of 17 O-labeled water distribution in the endolymphatic space of the posterior ampulla showed indistinct separation of endolymph and perilymph in the cochlea and most of the vestibule in all participants. Intralabyrinthine distribution of 17 O-labeled water differed from that in previous reports of intratympanically administered gadolinium-based contrast agent. 17 O-labeled water in the endolymphatic space may cause heavier endolymph and positional vertigo. These results of this study may add new insights for investigating the distribution and the effects of molecules in the inner ear after the intratympanic administration in living humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yoshida, Naganawa, Kobayashi, Sugimoto, Katayama, Nakashima, Kato, Ichikawa, Yamaguchi, Nishida and Sone.)

Purpose: To investigate the association of risk alleles in complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) with complement activation products in the aqueous humor in eyes with neovascular age-related macular degeneration (nAMD) including polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and pachychoroid neovasculopathy (PNV)., Design: Prospective, comparative, observational study., Participants: Treatment-naïve patients with nAMD and cataract patients as controls., Methods: The study included 236 eyes of 236 patients with nAMD and 49 control eyes of 49 patients. Aqueous humor samples were collected from 67 eyes with drusen-associated nAMD, 72 eyes with PCV, 26 eyes with RAP, and 71 eyes with PNV before intravitreal anti-VEGF injection and cataract surgery in the 49 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, and C5a using a bead-based immunoassay. Genotyping of the ARMS2 A69S (rs10490924), CFH I62V (rs800292), and CFH Y402H (rs1061170) was performed using TaqMan genotyping., Main Outcome Measures: The levels of complement activation products (C3a, C4a, and C5a) in the aqueous humor in each genotype of ARMS2 and CFH., Results: The C3a level in the aqueous humor was significantly elevated ( P  = 0.006) in patients with nAMD and the ARMS2 A69S risk allele, whereas the levels of the complement activation products were not associated with CFH I62V and Y402H genotypes. Among the control eyes, no significant differences were seen in any complement activation products for all genetic polymorphisms. The levels of the complement activation products in the aqueous humor of eyes with the nAMD subtypes for each genetic polymorphism did not show significant differences., Conclusions: The C3a concentration in the aqueous humor was significantly higher in Japanese nAMD patients with the ARMS2 A69S risk allele, whereas it was not elevated in the patients with CFH I62V. Age-related maculopathy susceptibility 2 A69S polymorphism is strongly associated with local complement activation in nAMD patients., (© 2022 by the American Academy of Ophthalmology.)

Ultrafast dynamic contrast-enhanced (UF-DCE) MRI is a new approach to capture kinetic information in the very early post-contrast period with high temporal resolution while keeping reasonable spatial resolution. The detailed timing and shape of the upslope in the time-intensity curve are analyzed. New kinetic parameters obtained from UF-DCE MRI are useful in differentiating malignant from benign lesions and in evaluating prognostic markers of the breast cancers. Clinically, UF-DCE MRI contributes in identifying hypervascular lesions when the background parenchymal enhancement (BPE) is marked on conventional dynamic MRI. This review starts with the technical aspect of accelerated acquisition. Practical aspects of UF-DCE MRI include identification of target hypervascular lesions from marked BPE and diagnosis of malignant and benign lesions based on new kinetic parameters derived from UF-DCE MRI: maximum slope (MS), time to enhance (TTE), bolus arrival time (BAT), time interval between arterial and venous visualization (AVI), and empirical mathematical model (EMM). The parameters derived from UF-DCE MRI are compared in terms of their diagnostic performance and association with prognostic markers. Pitfalls of UF-DCE MRI in the clinical situation are also covered. Since UF-DCE MRI is an evolving technique, future prospects of UF-DCE MRI are discussed in detail by citing recent evidence. The topic covers prediction of treatment response, multiparametric approach using DWI-derived parameters, evaluation of tumor-related vessels, and application of artificial intelligence for UF-DCE MRI. Along with comprehensive literature review, illustrative clinical cases are used to understand the value of UF-DCE MRI.

Purpose: Gold fiducial markers are used to guide liver stereotactic body radiation therapy (SBRT) and are hard to detect by magnetic resonance imaging (MRI). In this study, the parameters of the three-dimensional T1-weighted turbo gradient-echo (3D T1W-GRE) sequence were optimized for gold marker detection without degrading tumor delineation., Methods: Custom-made phantoms mimicking tumor and normal liver parenchyma were prepared and embedded with a gold marker. The 3D T1W-GRE was scanned by varying echo time (TE), bandwidth (BW), flip angle (FA), and base matrix size. The signal-to-noise ratio (SNR), contrast ratio (CR), and relative standard deviation (RSD) of the signal intensity in the area including the gold marker were evaluated, and the parameters were optimized accordingly. The modified 3D T1W-GRE (called HYBRID) was compared with the conventional T1W-GRE- and T2*-sequences in both phantom and clinical studies. In the clinical study of six patients with primary liver tumors, two observers visually assessed marker detection, tumor delineation, and overall image quality on a four-point scale., Results: In the phantom study, HYBRID showed significantly higher SNR and RSD than those of conventional T1W-GRE (P < 0.001). In the clinical study, HYBRID yielded significantly higher scores than conventional T1W-GRE did in terms of marker detection (P < 0.001). The scores of both sequences were not statistically different in terms of tumor delineation and overall image quality (P = 0.56 and P = 0.32)., Conclusions: The proposed HYBRID sequence improved gold fiducial marker detection without degrading tumor delineation in MRI for SBRT of primary liver tumor., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

We propose two methods to evaluate system-related distortion in magnetic resonance imaging (MRI) in radiation therapy treatment planning (RTP) and demonstrate the importance of three-dimensional (3D) distortion correction (DC) by quantitatively measuring the distortion magnitude. First, a small pin phantom was scanned at multiple positions using an external laser guide for accurate phantom placement and combined into one image encompassing a large area. Direct plane images were used for evaluating in-plane distortion and multiplanar reconstruction images for through-plane distortion with no DC, two-dimensional (2D) DC, and 3D DC. Second, a large grid sheet was scanned as the direct plane of the phantom placement. The distortion magnitude was determined by measuring the displacement between the MRI and reference coordinates. The measured distortions were compared between in- and through-plane when applying DC and between the two methods. The small pin phantom method can be used to evaluate a wide range of distortions, whereas data from the entire plane can be obtained with a single scan using the grid sheet without a laser guide. The mean distortion magnitudes differed between the methods. Furthermore, the 3D DC reduced in- and through-plane distortions. In conclusion, the small pin phantom method can be used to evaluate a wide range of distortions by creating a combined image, whereas the grid sheet method is simpler, accurate, repeatable, and does not require a special-order phantom or laser guide. As 3D DC reduces both in- and through-plane distortions, it can be used to improve RTP quality., Competing Interests: The authors declare that they have no conflict of interest.

Purpose: Equipment refurbishment was performed to remove the beam-hardening filter (BHF) from the CyberKnife system (CK). This study aimed to confirm the change in the beam characteristics between the conventional CK (present-BHF CK) and CK after the BHF was removed (absent-BHF CK) and evaluate the impact of BHF removal on the beam quality correction factors k Q ., Methods: The experimental measurements of the beam characteristics of the present- and absent-BHF CKs were compared. The CKs were modeled using Monte Carlo simulations (MCs). The energy fluence spectra were calculated using MCs. Finally, k Q were estimated by combining the MC results and analytic calculations based on the TRS-398 and TRS-483 approaches., Results: All gamma values for percent depth doses and beam profiles between each CK were less than 0.5 following the 3%/1 mm criteria. The percentage differences for tissue-phantom ratios at depths of 20 and 10 cm and percentage depth doses at 10 cm between each CK were -1.20% and -0.97%, respectively. The MC results demonstrated that the photon energy fluence spectrum of the absent-BHF CK was softer than that of the present-BHF CK. The k Q values for the absent-BHF CK were in agreement within 0.02% with those for the present-BHF CK., Conclusions: The photon energy fluence spectrum was softened by the removal of BHF. However, no remarkable impact was observed for the measured beam characteristics and k Q . Therefore, the previous findings of the k Q values for the present-BHF CK can be directly used for the absent-BHF CK., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF)., Methods: Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T 1 and T 2 values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance., Results: The signal intensity on the 3D-real IR image in each CSF region peaked at 4 h, and was decreased significantly by 24 h (P< 0.05). All patients had a maximum signal intensity at 4 h in the CPA, and Syl. The mean CPL signal intensity peaked at 4 h and decreased significantly by 24 h (P < 0.05). All patients but two had a maximum signal intensity at 4 h. Regarding the T 1 value in the cerebellar WM and GM, the T 1 value at 10 min post-IV-GBCA was significantly decreased compared to the pre-contrast scan, but no significant difference was observed at the other time points. There was no significant change in T 2 in the gray or white matter at any of the time points., Conclusion: Time course of GBCA after IV-SD-GBCA could be evaluated by 3D-real IR imaging in CSF spaces and in the brain by MRF.

Purpose: To investigate the characteristics of complement activation products and angiogenic cytokines in the aqueous humor in eyes with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD)., Methods: This was a prospective, comparative, observational study. All patients with choroidal neovascularization were classified as PNV without polyps, PNV with polyps (polypoidal choroidal vasculopathy [PCV]), or drusen-associated nAMD according to the presence or absence of pachychoroid features and soft drusen. This study included a total of 105 eyes. Aqueous humor samples were collected from 25 eyes with PNV without polyps, 23 eyes with PCV, and 24 eyes with drusen-associated nAMD before intravitreal anti-vascular endothelial growth factor (VEGF) injection and cataract surgery in 33 control eyes. Clinical samples were measured for complement component 3a (C3a), C4a, C5a, VEGF, and macrophage chemoattractant protein 1 (MCP-1) using a bead-based immunoassay., Results: C3a and MCP-1 levels were significantly higher in PCV (P = 0.032 and P = 0.039, respectively) and drusen-associated nAMD (P = 0.01 for both comparisons) than in controls, and no difference was seen in C3a and MCP-1 levels between PNV and controls (P = 0.747 and P = 0.294, respectively). VEGF levels were significantly higher in PNV (P = 0.016), PCV (P = 0.009), and drusen-associated nAMD (P = 0.043) than in controls. In PNV, the VEGF levels elevated without elevated C3a and MCP-1., Conclusions: PNV, PCV, and drusen-associated nAMD had significantly distinct profiles of complement activation products and cytokines in the aqueous humor.

Purpose: This study aimed to evaluate comprehensively; accuracy, repeatability and reproducibility of T 1 and T 2 relaxation times measured by magnetic resonance fingerprinting using B 1 + -corrected fast imaging with steady-state precession (FISP-MRF)., Methods: The International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) phantom was scanned for 100 days, and six healthy volunteers for 5 days using a FISP-MRF prototype sequence. Accuracy was evaluated on the phantom by comparing relaxation times measured by FISP-MRF with the reference values provided by the phantom manufacturer. Daily repeatability was characterized as the coefficient of variation (CV) of the measurements over 100 days for the phantom and over 5 days for volunteers. In addition, the cross-scanner reproducibility was evaluated in volunteers., Results: In the phantom study, T 1 and T 2 values from FISP-MRF showed a strong linear correlation with the reference values of the phantom (R 2 = 0.9963 for T 1 ; R 2 = 0.9966 for T 2 ). CVs were <1.0% for T 1 values larger than 300 ms, and <3.0% for T 2 values across a wide range. In the volunteer study, CVs for both T 1 and T 2 values were <5.0%, except for one subject. In addition, all T 2 values estimated by FISP-MRF in vivo were lower than those measured with conventional mapping sequences reported in previous studies. The cross-scanner variation of T 1 and T 2 showed good agreement between two different scanners in the volunteers., Conclusion: B 1 + -corrected FISP-MRF showed an acceptable accuracy, repeatability and reproducibility in the phantom and volunteer studies.

The majority of the models of emotional processing attribute subjective emotional feelings to physiological changes in the internal milieu, which are sensed by the interoceptive system. These physiological reactions evoked by emotional phenomena occur via the autonomic nervous system, and give rise to alterations in body-mind interactions that are characterized by heartbeat evoked magnetic fields (HEFs) involving brain regions associated with emotional perception. The current study used magnetoencephalography (MEG) to examine regional cortical activity and connectivity changes in HEFs provoked by the emotion of disgust. MEG results from 39 healthy subjects (22 female) revealed that passively listening to sounds of disgust elicited right insular cortical activity and enhancement of cortical connectivity between the right anterior ventral insular cortex and left ventromedial prefrontal cortex, demonstrated by phase lag indexes in the beta frequency range. Furthermore, inter-trial coherence significantly increased at 19 Hz and 23 Hz, and decreased at 14 Hz, which highlights the involvement of low beta oscillations in emotional processing. As these results were based on spontaneously triggered bioelectrical signals, more indigenous and induced signals were extracted with a block designed experiment. The insular cortices play an important role in emotional regulation and perception as the main cortical target for signals with interoceptive information, providing direct substrates of emotional feelings. The current results provide a novel insight into frequency properties of emotional processing, and suggest that emotional arousal evoked by listening to sounds of disgust partially impact the autonomic nervous system, altering HEFs via connectivity changes in the right anterior ventral insular cortex and left ventromedial prefrontal cortex., (Copyright © 2020 Kato, Takei, Umeda, Mimura and Fukuda.)

Aim: Nursing research worldwide is committed to rigorous scientific inquiry that provides a significant body of knowledge to advance nursing practice. One way to advance nursing practice is to increase the rate at which nursing research findings are translated into clinical practice, and one way to do that is to use pragmatic clinical trial research designs. This article aims to describe and advocate for the increased use of pragmatic clinical trials in nursing research and to provide a summary of one nursing pragmatic clinical trial., Methods: A review and discussion of the features of pragmatic clinical trials., Results: This article describes the principles and benefits of pragmatic clinical trials. Nurse researchers who use these principles will generate results that are more actionable, patient-centered, and relevant in clinical practice. Focusing on research that provides practical evidence that can be translated into evidence-based practice is an important way to improve the environment for nursing research that leads more rapidly to improved nursing practice., Conclusions: Embracing and increasing our use of pragmatic clinical trial design concepts in nursing research can enhance the significance of our findings and facilitate the translation of our research into practice., (© 2020 Japan Academy of Nursing Science.)

Background: Bipolar disorder (BD) is a serious psychiatric disorder that is associated with a high suicide rate, and for which no clinical biomarker has yet been identified. To address this issue, we investigated the use of magnetoencephalography (MEG) as a new prospective tool. MEG has been used to evaluate frequency-specific connectivity between brain regions; however, no previous study has investigated the frequency-specific resting-state connectome in patients with BD. This resting-state MEG study explored the oscillatory representations of clinical symptoms of BD via graph analysis., Methods: In this prospective case-control study, 17 patients with BD and 22 healthy controls (HCs) underwent resting-state MEG and evaluations for depressive and manic symptoms. After estimating the source current distribution, orthogonalized envelope correlations between multiple brain regions were evaluated for each frequency band. We separated regions-of-interest into seven left and right network modules, including the frontoparietal network (FPN), limbic network (LM), salience network (SAL), and default mode network (DMN), to compare the intra- and inter-community edges between the two groups., Results: In the BD group, we found significantly increased inter-community edges of the right LM-right DMN at the gamma band, and decreased inter-community edges of the right SAL-right FPN at the delta band and the left SAL-right SAL at the theta band. Intra-community edges in the left LM at the high beta band were significantly higher in the BD group than in the HC group. The number of connections in the left LM at the high beta band showed positive correlations with the subjective and objective depressive symptoms in the BD group., Conclusion: We introduced graph theory into resting-state MEG studies to investigate the functional connectivity in patients with BD. To the best of our knowledge, this is a novel approach that may be beneficial in the diagnosis of BD. This study describes the spontaneous oscillatory brain networks that compensate for the time-domain issues associated with functional magnetic resonance imaging. These findings suggest that the connectivity of the LM at the beta band may be a good objective biological biomarker of the depressive symptoms associated with BD., (Copyright © 2020 Sunaga, Takei, Kato, Tagawa, Suto, Hironaga, Ohki, Takahashi, Fujihara, Sakurai, Ujita, Tsushima and Fukuda.)

Purpose: To apply for detecting low-concentration gadolinium contrast agent (Gd), such as those in the perilymph and cerebrospinal fluid (CSF) at 4 h after intravenous administrations (IV), we tried to clarify the degree of increased signal intensity (SI) of low-concentration Gd by longer repetition time (TR) in heavily T 2 -weighed 3D-FLAIR., Materials and Methods: A phantom was designed using Gd diluted with saline at 0.250-0.008 mM and obtained images by varying the TR from 9000 to 16,000. We measured the SI of five slices for each concentration and compared the mean SI (SI mean ) values. Normalized SI (SI norm ) values, defined as the SI mean value of each TR divided by the SI mean value of 9000-ms TR for each concentration were compared., Results: Longer TR increased the SI mean values in all solutions. In the 0.250 mM solution, the SI mean value of 16,000-ms TR was 1.07-times greater than that of 9000-ms TR. In contrast, the SI mean value of 16,000-ms TR was 1.67-times greater than that of 9000-ms TR in 0.008 mM solution., Conclusion: SI increased with longer TR and lower Gd concentration. Thus, longer TR was useful in detecting low-concentration Gd, such as those in the perilymph and CSF at 4 h after IV.

We investigated how bacterial communities adapted to external resistances and exhibited the performance of electricity production in microbial fuel cells (MFCs) with external resistance of 10 Ω (LR-MFC) and 1000 Ω (HR-MFC). The HR-MFC exhibited better performance than the LR-MFC. The power densities of the LR-MFC and the HR-MFC were 5.2 ± 1.6 mW m -2 and 28 ± 9.6 mW m -2 after day 197, respectively. Low-scan cyclic voltammetry analyses indicated that the onset potential of the HR-MFC was more negative than that of the LR-MFC, suggesting that the higher external resistance led to enrichment of the highly current producing bacteria on the anode surface. All clones of Geobacter retrieved from the LR-MFC and the HR-MFC were members of the Geobacter metallireducens clade. Although the population density of Geobacter decreased from days 366-427 in the HR-MFC, the current density was almost maintained. Multidimensional scaling analyses based on denaturing gradient gel electrophoresis profiles indicated that the dynamics of the biofilm and anolytic communities changed synchronously in the two MFCs, but the dynamics of the bacterial communities in the LR-MFC and the HR-MFC were different from each other, reflecting different processes in adaptation to the different external resistances. The results suggest that the microbial community structure was formed by adapting to higher external resistance, exhibiting more negative onset potential and higher performance of the HR-MFC through collaborating with anode-respiring bacteria and fermenters., (Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion. Augmentation of glucose-dependent insulin secretion was abolished by adding a GPR40/FFAR1 antagonist. In mouse, insulinoma MIN6 cells, palmitic acid induced the activity of caspase 3/7 after a 72-h exposure, while pharmacologically active concentrations of MR1704 did not. In an oral glucose tolerance test in normal Sprague-Dawley rats, orally administered MR1704 (1-10 mg·kg -1 ) reduced plasma glucose excursion and enhanced insulin secretion, but MR1704 did not induce hypoglycemia, even at 300 mg·kg -1 , in fasted Sprague-Dawley rats. In addition, orally administered MR1704 reduced plasma glucose excursion and enhanced insulin secretion in diabetic Goto-Kakizaki rats. Oral administration of MR1704 once daily to Goto-Kakizaki rats reduced their blood glucose levels during a 5-week treatment period without reducing pancreatic insulin content; as a result, hemoglobin A1C levels significantly decreased. These results suggest that MR1704 improves glucose homeostasis through glucose-dependent insulin secretion with a low risk of hypoglycemia and pancreatic toxicity. MR1704 shows promise as a new, glucose-lowering drug to treat type 2 diabetes mellitus., (© 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

When working with liposomes analogous to cell membranes, it is important to develop substrates that can regulate interactions with the liposome surface in response to light. We achieved a photo-triggered release from liposomes by using a copolymer of poly(vinyl alcohol) carrying a malachite green moiety (PVAMG). Although PVAMG is a neutral polymer under dark conditions, it is photoionized upon exposure to UV light, resulting in the formation of a cationic site for binding to liposomes with a negatively charged surface. Under UV irradiation, PVAMG showed effective interaction with liposomes, releasing the encapsulated compound; however, this release was negligible under dark conditions. The poly(vinyl alcohol) moiety of PVAMG played an important role in the photo-triggered release. This release was caused by membrane destabilization without lipid solubilization. We also investigated different aspects of liposome/PVAMG interactions, including PVAMG-induced fusion between the liposomes and the change in the liposome morphologies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Emotion recognition deficits emerge with the increasing age, in particular, a decline in the identification of sadness. However, little is known about the age-related changes of emotion processing in sensory, affective, and executive brain areas. This functional magnetic resonance imaging (fMRI) study investigated neural correlates of auditory processing of prosody across adult lifespan. Unattended detection of emotional prosody changes was assessed in 21 young (age range: 18-35 years), 19 middle-aged (age range: 36-55 years), and 15 older (age range: 56-75 years) adults. Pseudowords uttered with neutral prosody were standards in an oddball paradigm with angry, sad, happy, and gender deviants (total 20% deviants). Changes in emotional prosody and voice gender elicited bilateral superior temporal gyri (STG) responses reflecting automatic encoding of prosody. At the right STG, responses to sad deviants decreased linearly with age, whereas happy events exhibited a nonlinear relationship. In contrast to behavioral data, no age by sex interaction emerged on the neural networks. The aging decline of emotion processing of prosodic cues emerges already at an early automatic stage of information processing at the level of the auditory cortex. However, top-down modulation may lead to an additional perceptional bias, for example, towards positive stimuli, and may depend on context factors such as the listener's sex.

Since the discovery of mirror neuron system, several neurophysiological and neuroimaging studies showed that the mirror neuron system might have a role in understanding other people's actions and intentions with automatic simulation of their actions. Moreover, some studies suggested that mirror neurons have a broader role in social cognition including understanding others' emotions and empathy. It has not been proved, however, whether the mirror neuron system is necessarily involved in empathy processes. In the domain of social cognition deficits, it is important to investigate the involvement of mirror neuron system dysfunction in psychosis such as schizophrenia. Using magnetoencephalography, we examined whether antipsychotic-free schizophrenia patients displayed mirror neuron system dysfunction during observation of biological motion (jaw movement). Compared with normal controls, the patients with schizophrenia had fewer components of both the waveform and equivalent current dipole, suggesting aberrant brain activity resulting from dysfunction of the right inferior parietal cortex. They also lacked the changes of alpha band and gamma band oscillation seen in normal controls, and had weaker phase locking factors and gamma-synchronization predominantly in right parietal cortex. This finding demonstrated that untreated patients with schizophrenia exhibited aberrant mirror neuron system function based on the right inferior parietal cortex, which is characterized by dysfunction of gamma-synchronization.

This study examines the attitudes of young Japanese, Chinese, and South Koreans toward birth and child-rearing. The survey targeted four-year university students (n＝1,668) who responded to an anonymous survey using self-report questionnaires between December 2012 and April 2013. The collection rates were 72.5%, 94.7%, and 96.5% for the Japanese, Chinese, and South Korean students, respectively. Correlations among the respondents' attributes, medical and scientific literacy levels, and views of preferred qualities of children were analyzed using chi-square test, supplemented by residual analysis (significance level set at p＜0.05). Participants were asked whether they were willing to use the following methods for obtaining preferred qualities in their children:(1) choosing a spouse (43.2%, 72.6%, and 85.1% of the Japanese, Chinese, and South Koreans, respectively, agreed);(2) using a sperm bank (cryobank) (5.8%, 60.1%, and 81.7% of the Japanese, Chines, and South Koreans, respectively, agreed);and (3) using an egg cell bank (ova bank or cryobank) (5.3%, 47.2%, and 70.3% of the Japanese, Chinese, and South Koreans, respectively, agreed). The proportion of affirmative responses (indicating "eugenic inclination") to these statements was significantly higher among the Chinese and South Korean participants than their Japanese counterparts (p＜0.001). Significant differences were also found in the attitudes of the 3 groups toward methods for obtaining the preferred qualities for their children:prenatal diagnosis, pre-implantation diagnosis, the environment during pregnancy, and child-rearing.

The green ciliate Paramecium bursaria contains several hundred symbiotic Chlorella species. We previously reported that symbiotic algal carbon fixation is enhanced by P. bursaria extracts and that the enhancing factor is a heat-stable, low-molecular-weight, water-soluble compound. To identify the factor, further experiments were carried out. The enhancing activity remained even when organic compounds in the extract were completely combusted at 700 degrees C, suggesting that the factor is an inorganic substance. Measurement of the major cations, K+, Ca2+, and Mg2+, by an electrode and titration of the extract resulted in concentrations of 0.90 mM, 0.55 mM, and 0.21 mM, respectively. To evaluate the effect of these cations, a mixture of the cations at the measured concentrations was prepared, and symbiotic algal carbon fixation was measured in the solution. The results demonstrated that the fixation was enhanced to the same extent as with the P. bursaria extract, and thus this mixture of K+, Ca2+, and Mg2+ was concluded to be the carbon fixation-enhancing factor. There was no effect of the cation mixture on free-living C. vulgaris. Comparison of the cation concentrations of nonsymbiotic and symbiotic Paramecium extracts revealed that the concentrations of K+ and Mg2+ in nonsymbiotic Paramecium extracts were too low to enhance symbiotic algal carbon fixation, suggesting that symbiotic P. bursaria provide suitable cation conditions for photosynthesis to its symbiotic Chlorella.

The aim of this paper is to introduce some characteristics of the historical as well as current situation of nanotech research and development in Japan in particular including regulations, and to discuss how ethical issues of nanotechnology should be addressed or how the ethics of nanotechnology should be constructed to fit the situation. The first part will center around the strength and weakness of Japan's nanotech R&D (research and development) and new circumstances which nanotechnology has prompted in Japan and alongside which nanotechnology has arrived (especially interdisciplinarity). The following prescriptive argument will, based on the descriptive account, question how to address ethical issues of nanotechnology, taking into consideration the nature of nanotech R&D, namely continuity, uniqueness, international dimension and political intervention, citing the example of the pharmaceutical industry. I will argue that international cooperation in the form of mutual reference to, replication of and the integration of guidelines and regulations, can enhance cost-effectiveness to ensure the comprehensiveness of regulatory measures.

Symbiotic Chlorella F36-ZK isolated from Paramecium bursaria F36 has constitutive amino acid transport systems, whereas free-living Chlorella does not. We found that in symbiotic algae, the rate of serine (Ser) uptake increased in the presence of glucose (Glc) and non-metabolisable analogues, whilst incorporation of Ser into protein was not affected. The activation did not involve new protein synthesis and was enhanced under alkaline conditions. An increase in the rate of Ser transport resulted from Glc treatment even when pulsed for only 1 min at low concentrations (EC(50)=3 microM). No uptake of Glc itself was observed in F36-ZK. Thus, the transport signal appears to be transmitted via a glucose sensing and signalling pathway. Many Glc-related compounds also increased the rate of Ser uptake without an additive effect, suggesting recognition of these sugars by the same receptor and providing some insight into features of the structure-activity relationship. Ser uptake by F36-ZK is inhibited by Ca(2+), which is typically considered to be a positive modulator of amino acid uptake. Given that Glc restored Ser uptake from inhibition by Ca(2+), we propose that this compound is possibly involved in regulation of amino acid transport in this symbiotic relationship.

Since beta-tryptase is considered a critical mediator of asthma, potent tryptase inhibitors may be useful as new agents for the treatment of asthma. We investigated 4-substituted benzylamine derivatives and obtained M58539 (15h) as a potent inhibitor of beta-tryptase (IC50 = 5.0 nM) with high selectivity against other serine proteases, low molecular weight, clog P value less than 5, lack of amidino and guanidino groups, and independence of Zn2+ ion.

We previously reported an orally active anti-allergic agent, M50367, modulated Th1/Th2 balance to down-regulate Th2 response in a murine model of atopic asthma. In this study, we examined the effect of M50354, the active metabolite of M50367, on the differentiation of naïve Th cells into Th1/Th2 cells. M50354 at 3 microM decreased the generation of Th2 cells by 0.2-fold and increased that of Th1 cells by 1.6-fold from naïve Th cells primed with antigenic peptide and antigen-presenting cells. Its effect was also seen when naïve Th cells were primed with anti-T cell receptor and anti-CD28 agonistic antibodies instead of antigen and antigen-presenting cells. M50354 decreased early endogenous IL-4 production in the nai;ve Th cell priming culture without affecting interferon-gamma production and proliferation. In contrast, M50354 had no effect on interferon-gamma and IL-4 production from mature Th1 and Th2 cells. These results suggest that M50354 directly acts on naïve Th cells to suppress their differentiation into Th2 cells.