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Background: In recent years, left ventricular hypertrophy and cardiac dysfunction have been reported in human and canine patients with hypercortisolism (HAC) and in dogs treated experimentally with high-dose prednisolone. However, to our knowledge, there have been no reports on the effects of hyperglucocorticism (HGC) on the mitral valve (MV). Aim: This study aimed to compare the MV in dogs treated with high-dose prednisolone with that in healthy dogs to investigate the effects of HGC on the MV. Methods: We investigated the effects of HGC on the MV by comparing samples obtained from high-dose glucocorticoid-treated (P) and healthy (C) dogs. The P group included healthy Beagle dogs (n = 6) treated with prednisolone (2 mg/kg, bid, po) for 84 days and the C group included healthy Beagle dogs (n = 6) euthanized for unrelated reasons. The anterior and posterior mitral leaflets (AML and PML, respectively) from both groups were harvested and stained with hematoxylin–eosin, Alcian blue, and Masson trichome. Additionally, adiponectin (ADN) and glucocorticoid receptor immunohistochemistry were performed. Histological evaluation was performed in the atrialis, spongiosa, fibrosa, and all layers of the proximal, middle, and distal regions of the AML and PML. Results: The proportion of the spongiosa layer thickness to the total thickness was higher in the P than in the C group (proximal and middle AML). However, the proportion of the fibrosa layer thickness to the total thickness was lower in the P than in the C group (middle PML). Areas of acidic sulfated mucosubstance deposition were smaller in the fibrosa layer and all layers (middle AML), while those of collagen deposition were smaller in the spongiosa and total layers (proximal and middle AML), in the P than in the C group. Additionally, ADN expression in the spongiosa layer was higher in the P than in the C group (middle AML). Conclusion: These findings suggest that long-term administration of synthetic glucocorticoids induces histological changes in the MV. These changes may lead to MV dysfunction in dogs with HGC. [Open Vet J 2023; 13(2.000): 150-170]

Abstract Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18–9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/μL), non-deviated κ/λ ratio (0.1–10), lower B2MG (

Abstract Metal homeostasis is tightly regulated in cells and organisms, and its disturbance is frequently observed in some diseases such as neurodegenerative diseases and metabolic disorders. Previous studies suggest that zinc and iron are necessary for the normal functions of pancreatic β cells. However, the distribution of elements in normal conditions and the pathophysiological significance of dysregulated elements in the islet in diabetic conditions have remained unclear. In this study, to investigate the dynamics of elements in the pancreatic islets of a diabetic mouse model expressing human islet amyloid polypeptide (hIAPP): hIAPP transgenic (hIAPP-Tg) mice, we performed imaging analysis of elements using synchrotron scanning X-ray fluorescence microscopy and quantitative analysis of elements using inductively coupled plasma mass spectrometry. We found that in the islets, zinc significantly decreased in the early stage of diabetes, while iron gradually decreased concurrently with the increase in blood glucose levels of hIAPP-Tg mice. Notably, when zinc and/or iron were decreased in the islets of hIAPP-Tg mice, dysregulation of glucose-stimulated mitochondrial respiration was observed. Our findings may contribute to clarifying the roles of zinc and iron in islet functions under pathophysiological diabetic conditions.

Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform a basic analysis of the anti-tumor effect of talaporfin sodium (TS)-PDT as well as its synergism with the immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate the cell death mechanism induced by TS-PDT and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT in vitro. We establish a syngeneic mouse model of bilateral flank tumors and verify the enhancement of the abscopal effect on the non-irradiated side. TS-PDT induced apoptosis, necrosis, and autophagy-associated cell death in vitro. TS-PDT induced the release and/or expression of DAMPs in vitro. Tumor growth was inhibited in the TS-PDT and anti-PD-1 antibody combination group compared with other single-treatment or non-treatment groups in vivo. In summary, TS-PDT induces the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhances the anti-tumor immunity induced by TS-PDT. Thus, our results demonstrate that the combination of TS-PDT and anti-PD-1 antibody can potentially be used for anti-tumor therapy.

Intensity-modulated signals have the advantage of being directly detectable by the image sensor but have the drawback that the signal quality is easily deteriorated by crosstalk noise, in contrast to phase-modulated signals. In order to suppress the crosstalk noise, we propose a new signal arrangement for multilevel intensity-modulated signals. The concept of our method is to reduce the number of adjacent pixels that are a source of inter-pixel crosstalk noise and to minimize intensity modulation owing to interference with crosstalk noise. We have numerically and experimentally demonstrated that our method can reduce the error rate and improve the recording density compared to the conventional signal arrangement. Our proposed method offers a promising solution for achieving higher recording densities in intensity-modulated holographic data storage systems.

Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is a form of nociplastic pain. A standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this study is to evaluate the effectiveness of Rikkosan—a traditional Japanese herbal medicine (Kampo)—in the treatment of BMS. A single-center retrospective study was conducted on 20 patients who were diagnosed with BMS and treated with Rikkosan alone (total daily dose; 7.5 g) three times daily for approximately 4 weeks (29.5 ± 6.5 days). Rikkosan was dissolved in hot water and taken internally. They had an average age of 63 years, and 90% were being treated for other illnesses, but their medication status was the same during this study period, except for Rikkosan. No adverse events were observed in patients. Numerical rating scale (NRS) or visual analog scale (VAS)/10 scores decreased significantly between the time of the initiation of Rikkosan and one month after (−2.1 ± 1.2, p < 0.05). Rikkosan has a short-term effect of reducing NRS by two levels in BMS patients.

Background and Objectives: Despite the fact that biologic drugs have transformed inflammatory bowel disease (IBD) treatment, addressing fibrosis-related strictures remains a research gap. This study explored the roles of cytokines, macrophages, and Krüppel-like factors (KLFs), specifically KLF4, in intestinal fibrosis, as well as the interplay of KLF4 with various gut components. Materials and Methods: This study examined macrophage subtypes, their KLF4 expression, and the effects of KLF4 knockdown on macrophage polarization and cytokine expression using THP-1 monocyte models. Co-culture experiments with stromal myofibroblasts and a conditioned medium from macrophage subtype cultures were conducted to study the role of these cells in intestinal fibrosis. Human-induced pluripotent stem cell-derived small intestinal organoids were used to confirm inflammatory and fibrotic responses in the human small intestinal epithelium. Results: Each macrophage subtype exhibited distinct phenotypes and KLF4 expression. Knockdown of KLF4 induced inflammatory cytokine expression in M0, M2a, and M2c cells. M2b exerted anti-fibrotic effects via interleukin (IL)-10. M0 and M2b cells showed a high migratory capacity toward activated stromal myofibroblasts. M0 cells interacting with activated stromal myofibroblasts transformed into inflammatory macrophages, thereby increasing pro-inflammatory cytokine expression. The expression of IL-36α, linked to fibrosis, was upregulated. Conclusions: This study elucidated the role of KLF4 in macrophage polarization and the intricate interactions between macrophages, stromal myofibroblasts, and cytokines in experimental in vitro models of intestinal fibrosis. The obtained results may suggest the mechanism of fibrosis formation in clinical IBD.

Oxidation of silicon carbide (SiC) is known to induce defects at the interface of the SiO2/SiC system. NO-annealing is a standard industrial method of nitridation, but oxidation may progress during NO-nitridation, which may generate interface defects. Here, we propose a new method of fabricating SiO2/SiC metal-oxide-semiconductor (MOS) devices: sputter deposition of SiO2 in an Ar/N2 gas mixture followed by high-temperature CO2-post deposition annealing to form SiO2 and incorporate nitrogen at the interface while suppressing oxidation of the SiC. We obtained the nitrogen depth profile by performing x-ray photoelectron spectroscopy and confirmed that most of the nitrogen atoms exist at the abrupt interface. While maintaining a low interface state density and good insulating property, we demonstrated much improved reliability of MOS devices compared to conventional NO-annealed samples, thanks to the well-designed SiO2/SiC interface by the proposed method.

Abstract Wearable technologies are becoming important for the fields of information technology and healthcare, driven mainly by societal issues such as the aging society and the current pandemic. Recently developed flexible/stretchable wearable devices have demonstrated their ability for long‐term healthcare monitoring with improved signal integrity and multimodality. However, the adherence of wearers to such wearable devices cannot be determined only by the function. Here “comfort‐of‐wear” is identified as one of the most critical parameters for future wearables, similar to how clothes are chosen based on how comfortable they are. “Comfort‐of‐wear” is defined as the device's ability to not to disturb the wearers’ daily life. Several engineering approaches are introduced to improve the comfort‐of‐wear of devices—via strategies that include improving flexibility by utilizing a combination of structures, materials, and systems. Finally, the future of wearables enabled by cutting‐edge advanced electronic technologies is proposed.

This dataset, produced through the Coordinated Ocean Wave Climate Project (COWCLIP) phase 2, represents the first coordinated multivariate ensemble of 21st Century global wind-wave climate projections available (henceforth COWCLIP2.0). COWCLIP2.0 comprises general and extreme statistics of significant wave height (HS), mean wave period (Tm), and mean wave direction (θm) computed over time-slices 1979-2004 and 2081-2100, at different frequency resolutions (monthly, seasonally and annually). The full ensemble comprising 155 global wave climate simulations is obtained from ten CMIP5-based state-of-the-art wave climate studies and provides data derived from alternative wind-wave downscaling methods, and different climate-model forcing and future emissions scenarios. The data has been produced, and processed, under a specific framework for consistency and quality, and follows CMIP5 Data Reference Syntax, Directory structures, and Metadata requirements. Technical comparison of model skill against 26 years of global satellite measurements of significant wave height has been undertaken at global and regional scales. This new dataset provides support for future broad scale coastal hazard and vulnerability assessments and climate adaptation studies in many offshore and coastal engineering applications.

Background: Most patients with idiopathic growth hormone deficiency (iGHD) in childhood have normal GH stimulation test results in adulthood. The present study aimed to investigate the characteristics and possible etiology of transient iGHD. Methods: Patients with childhood-onset iGHD who completed their GH treatment between March 2010 and March 2021 were retrospectively studied. Patients with a clear history of child abuse or constitutional delay of growth and puberty were excluded. Ten patients with a diagnosis of iGHD based on a decreased growth rate and growth hormone stimulation test findings at the time of onset were included. Retesting demonstrated that these patients had a normal GH level. Results: Five patients had insufficient weight gain (BMI SD score < −1.0 at the start of treatment or a decrease in BMI SD score > 1.0 from one year before treatment to the start of treatment). The other five patients had no remarkable clinical features. One patient had decreased height velocity at the same time as their sibling. Conclusion: Insufficient pre-treatment weight gain or a familial cluster of cases may be related to low GH peaks of GHST, leading to a diagnosis of transient GHD.

The purpose of this study was to clarify the characteristics of lower-extremity kinematics during the running of soccer players with chronic ankle instability (CAI) in comparison to those without CAI. Twenty-two male college soccer players participated in this study. Twelve players were assigned to the CAI group and ten players to the non-CAI group, and players were diagnosed according to the Cumberland Ankle Instability Tool. Kinematic data of the hip, knee, ankle, foot, and ground reaction force components during the stance phase of running were obtained using a three-dimensional motion analysis system. The results revealed that soccer players with CAI who landed with ankle inversion and other characteristic kinematics in their lower extremity during the stance phase of running were similar to those without CAI. These results show that running kinematics in soccer players are not affected by the presence or absence of CAI. Future studies based on the results of this study may contribute to the analysis of the risk of developing CAI during soccer and may also help prevent lateral ankle sprains.

Abstract We evaluated the long-term (24-month) efficacy of a novel individualized treatment protocol with 2 mg aflibercept for treatment-naive BRVO with macular edema. Each patient received an initial aflibercept injection and was then examined every 2 weeks until recurrence of edema. At recurrence, each patient received a second injection of aflibercept. The period of efficacy was defined as the time between the first and second injections. Subsequently, each patient was examined and re-injected with aflibercept at their personalized treatment interval, which was defined as 1 week shorter than the period of efficacy. Thirty-seven eyes of 48 patients showed recurrence after the initial injection. The mean period of efficacy was 92.5 ± 40.8 days, and the mean number of visits before recurrence, 7.6 ± 2.9. The mean 24-month best corrected visual acuity (BCVA) was significantly better than the mean baseline BCVA but significantly worse than the best BCVA during the period of efficacy. The mean gain of BCVA at 24 months was 0.07 ± 0.18 logMAR. The mean 24-month central macular thickness (CMT) was significantly lower than the mean baseline CMT but showed no difference from the mean best CMT (p = 0.060). The mean total number of visits during the 24 months was 15.8 ± 3.4. We conclude that the individualized treatment protocol that was based on the period of efficacy in treatment-naïve BRVO eyes with macular edema achieved satisfactory long-term visual outcome.

Abstract Background Embolic stroke of undetermined source (ESUS) encompasses diverse embologenic mechanisms, which transesophageal echocardiography (TEE) is critical to detect. Specific markers related to each embolic source in ESUS is not fully studied. We focused on D-dimer levels, and explored the association of D-dimer with potential embolic sources (PES) identified on TEE in ESUS. Methods Consecutive patients with ESUS were included in this study. Clinical characteristics including D-dimer levels were compared between ESUS patients with and without TEE, and among none of, one, and at least two PES in ESUS patients undergoing TEE. Factors related to elevation of D-dimer were analyzed. Results A total of 211 patients (age, 69.3 ± 13.2 years; 149 males) with ESUS were enrolled. Of these, 115 received TEE, displaying significantly younger age and lower D-dimer levels than patients without TEE (P