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Licorice is a crude drug that is used in traditional Japanese Kampo medicine and is also used as a sweetener. Occasionally, it causes pseudoaldosteronism (PsA) as a side effect. The major symptoms include hypokalemia, hypertension, edema, and low plasma aldosterone levels. PsA might be caused by the metabolites of glycyrrhizinic acid (GL), a component of licorice. The development of PsA markedly varies among individuals; however, the factors that cause these individual differences remain unknown. In this study, 78 patients who consumed Kampo medicines containing licorice were enrolled, and their laboratory data, including serum potassium levels, plasma aldosterone concentrations (PAC), and the concentrations of GL metabolites in the residual blood and/or urine samples were evaluated. Of the 78 participants, 18 β -glycyrrhetinic acid (GA), 3- epi -GA, 3-oxo-GA, 18 β -glycyrrhetinyl-30- O -glucuronide (GA30G), and 3 -epi- GA30G were detected in the serum samples of 65, 47, 63, 62, and 3 participants, respectively. Of the 29 urine samples collected, GA30G and 3 -epi -GA30G were detected in 27 and 19 samples. 3- epi -GA30G is a newly found GL metabolite. Moreover, 3 -epi- GA, 3-oxo-GA, and 3- epi -GA30G were identified in human samples for the first time. High individual differences were found in the appearances of 3- epi -GA in serum and 3- epi -GA30G in urine, and the concentrations of these metabolites were correlated with serum PsA markers. The inhibitory titers of 3- epi -GA, 3-oxo-GA, GA30G, and 3 -epi- GA30G on human 11 β -hydroxysteroid dehydrogenase type 2 (11 β -HSD2) were almost similar. These findings suggest that 3 -epi- GA and/or 3- epi -GA30G are associated with individual differences in the development of PsA. Significance Statement In this study, we detected 3- epi -GA in human serum for the first time. We also identified 3- epi -GA30G as a novel GL metabolite in human urine. These GL metabolite levels showed correlations with markers of PsA. Additionally, there are individual differences in whether or not they appear in the serum/urine. In conclusion, 3- epi -GA/3- epi- GA30G correlates with individual differences in the development of PsA., (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.)

This study aimed to assess ginger extract's impact on ocular and peripheral blood flow and its potential to alleviate eye fatigue and shoulder stiffness. This study included 100 healthy individuals aged 20-73 years with eye fatigue and shoulder stiffness. Participants were randomly assigned to receive either placebo capsules or ginger extract capsules daily for eight weeks. Ocular blood flow, peripheral blood flow, eye fatigue (visual analog scale [VAS]), shoulder stiffness (VAS), body warmth (VAS), and shoulder muscle stiffness were assessed at weeks 0, 4, and 8, respectively. No improvement in ocular blood flow was observed under the study conditions. Conversely, peripheral blood flow in deep areas was enhanced in females ( p = 0.033). Subgroup analysis by age (≥51 or <51 years) revealed that ginger's effect on enhancing peripheral blood flow in deep vessels was restricted in females under 51 ( p = 0.017). Similarly, subjective complaints of eye fatigue and shoulder stiffness were improved by ginger consumption in females under 51. Body warmth was favorably changed significantly in males ≥51 years due to ginger consumption. The muscle stiffness showed no statistically significant changes. In conclusion, ginger consumption reduces eye fatigue and shoulder stiffness by enhancing peripheral blood flow in relatively young females.

Skin color observation provides a simple and non-invasive method to estimate the health status of patients. Capillary Refill Time (CRT) is widely used as an indicator of pathophysiological conditions, especially in emergency patients. While the measurement of CRT is easy to perform, its evaluation is highly subjective. This study proposes a method to aid quantified CRT measurement using an RGB camera. The procedure consists in applying finger compression to the forearm, and the CRT is calculated based on the skin color change after the pressure release. We estimate compression applied by a finger from its fingernail color change during compression. Our study shows a step towards camera-based quantitative CRT for untrained individuals., Competing Interests: Conflicts of Interest None., (Copyright © 2024. Published by Elsevier Ltd.)

In this paper, we propose a noise-robust pulse wave estimation method from near-infrared face video images. Pulse wave estimation in a near-infrared environment is expected to be applied to non-contact monitoring in dark areas. The conventional method cannot consider noise when performing estimation. As a result, the accuracy of pulse wave estimation in noisy environments is not very high. This may adversely affect the accuracy of heart rate data and other data obtained from pulse wave signals. Therefore, the objective of this study is to perform pulse wave estimation robust to noise. The Wiener estimation method, which is a simple linear computation that can consider noise, was used in this study. Experimental results showed that the combination of the proposed method and signal processing (detrending and bandpass filtering) increased the SNR (signal to noise ratio) by more than 2.5 dB compared to the conventional method and signal processing. The correlation coefficient between the pulse wave signal measured using a pulse wave meter and the estimated pulse wave signal was 0.30 larger on average for the proposed method. Furthermore, the AER (absolute error rate) between the heart rate measured with the pulse wave meter was 0.82% on average for the proposed method, which was lower than the value of the conventional method (12.53% on average). These results show that the proposed method is more robust to noise than the conventional method for pulse wave estimation.

This was a preliminary retrospective study to clarify the effectiveness of traditional Japanese acupuncture on the stress level of Japanese expatriates who studied or worked in Myanmar. Total 22 Japanese expatriate patients were selected for this study. The profile of mood states second edition-adult short form scale was used to evaluate the stress-relief effect of acupuncture before every treatment. Negative mood (tension and confusion) and total mood disturbances significantly decreased after acupuncture treatment. Regarding the influence of background, the experience of staying abroad significantly influenced the efficacy of the acupuncture treatment. These results indicate that acupuncture treatment can relieve stress experienced by Japanese expatriates. The results also suggest that the experience of staying abroad might be one of the leading factors that can modulate the effects of treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Optic nerve head (ONH) blood flow decrease without changes in intraocular pressure in a possible rat model of retinal ganglion cell loss by systemic administration of aldosterone. To compare the blood flow in the ONH, using laser speckle flowgraphy (LSFG), in healthy eyes and in eyes with primary aldosteronism (PA)., Methods: The ONH tissue area mean blur rate (MT) was evaluated in this single center, retrospective, cross-sectional study using LSFG. In order to compare the MT between PA patients and normal subjects, mixed-effects models were used, with adjustments made for the mean arterial pressure, disc area, and β-peripapillary atrophy (β-PPA) area. Mixed-effects models were also used to analyze the risk factors affecting the MT., Results: This study evaluated a total of 29 eyes of 17 PA patients and 61 eyes of 61 normal subjects. There was a significantly lower MT in PA patients (10.8 ± 0.4) as compared to the normal subjects (12.3 ± 0.3) (P = 0.004). The MT was significantly lower in PA patients (10.8 ± 0.6) even after adjusting for the potential confounding factors when compared to normal subjects (12.3 ± 0.3) (P = 0.046). Multivariate mixed-effects model analysis demonstrated that the MT was significantly associated with the PA and β-PPA., Conclusions: There was a significantly lower ONH blood flow in PA patients as compared to normal subjects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hirooka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We propose a remote method to estimate continuous blood pressure (BP) based on spatial information of a pulse-wave as a function of time. By setting regions of interest to cover a face in a mutually exclusive and collectively exhaustive manner, RGB facial video is converted into a spatial pulse-wave signal. The spatial pulse-wave signal is converted into spatial signals of contours of each segmented pulse beat and relationships of each segmented pulse beat. The spatial signal is represented as a time-continuous value based on a representation of a pulse contour in a time axis and a phase axis and an interpolation along with the time axis. A relationship between the spatial signals and BP is modeled by a convolutional neural network. A dataset was built to demonstrate the effectiveness of the proposed method. The dataset consists of continuous BP and facial RGB videos of ten healthy volunteers. The results show an adequate estimation of the performance of the proposed method when compared to the ground truth in mean BP, in both the correlation coefficient (0.85) and mean absolute error (5.4 mmHg). For comparison, the dataset was processed using conventional pulse features, and the estimation error produced by our method was significantly lower. To visualize the root source of the BP signals used by our method, we have visualized spatial-wise and channel-wise contributions to the estimation by the deep learning model. The result suggests the spatial-wise contribution pattern depends on the blood pressure, while the pattern of pulse contour-wise contribution pattern reflects the relationship between percussion wave and dicrotic wave., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Japanese traditional (Kampo) medicine has been empirically used for nocturnal enuresis (NE). This study aims to investigate the efficacy of one of the most popular formulas, shokenchuto (SKT). We retrospectively analyzed 110 patients with NE who were referred to our department. Following the diagnosis of NE, treatment was started with either alarm or/and desmopressin (DDAVP) therapy. Patient refractory to DDAVP monotherapy or to combination therapy consisting of DDAVP and bedwetting alarm were selected. SKT (Tsumura Co., Tokyo, Japan) extract at a dose of 2.5 g was administered orally to all intractable cases twice daily before meals. The treatment outcomes and safety were assessed. In total, 24 cases were patient refractory to DDAVP monotherapy or to combination therapy consisting of DDAVP and bedwetting alarm. SKT was highly effective in 8, effective in 7, and ineffective in 9. A significant difference was observed between ages 10 and over (P = 0.031). SKT was significantly effective as a treatment for NE in patients aged ≥10 years and could be a good alternative if alarm or DDAVP therapies are ineffective. We proposed evaluating SKT prospectively for NE., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

It is expected that a low-toxicity natural compound like Kampo formulas would exhibit a preventive effect on COVID-19, in a global outbreak of coronavirus disease 2019 (COVID-19). Although the biological properties and safety of the representative Kampo, Hochuekkito (HET), and Kakkonto (KKT) have been confirmed in various animal model experiments and clinical studies, and in a few human studies to induce biological effects on various infectious diseases without significant toxicity, it is unclear whether HET and KKT are safe and effective for COVID-19 prevention. We summarized the clinical characteristics of HCWs and the preventive effects of HET and KKT. We performed a retrospective, single-center, cohort study that included 175 HCWs (aged 21-77 years) from a total number of 217 in a hospital with a history of COVID-19 cluster infection. In total, 175 HCWs were tested for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. We identified 27 patients (median age: 49 ± 10.7 years) who were diagnosed with COVID-19. The patients in the group that had a body mass index ≥ 25 had a high COVID-19 infection risk, while those in the group with a Kampo formula adherence rate ≥ 40% had a low COVID-19 risk. Patients in the group with an adherence rate ≥ 40%, as well as those in the current alcohol consumption group, were at a low risk of developing severe COVID-19. In conclusion, HET and KKT may have prevented the onset or worsening of COVID-19, which could be clinically used. Obesity might have increased the patients' susceptibility to COVID-19 and the disease severity., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Colored product textures correspond to particle size distributions. The microscopic images of colorants must be divided into regions to determine the particle size distribution. The conventional method used for this process involves manually dividing images into areas, which may be inefficient. In this paper, we have overcome this issue by developing two different modified architectures of U-Net convolution neural networks to automatically determine the particle sizes. To develop these modified architectures, a significant amount of ground truth data must be prepared to train the U-Net, which is difficult for big data as the labeling is performed manually. Therefore, we also aim to reduce this process by using incomplete labeling data. The first objective of this study is to determine the accuracy of our modified U-Net architectures for this type of image. The second objective is to reduce the difficulty of preparing the ground truth data by testing the accuracy of training on incomplete labeling data. The results indicate that efficient segmentation can be realized using our modified U-Net architectures, and the generation of ground truth data can be simplified. This paper presents a preliminary study to improve the efficiency of determining particle size distributions with incomplete labeling data.

Several traditional Japanese Kampo formulas are known to have inhibitory effects on infections with viruses that cause respiratory symptoms. Although some herbs and their components have been reported to suppress SARS-CoV-2 replication in vitro , it is difficult to compare effective Kampo formulas because of the different methods used in studies. Thus, we carried out in vitro experiments on the suppression of SARS-CoV-2 infection by Kampo formulas and crude drugs used for the common cold to compare their suppressive effects on virus infection. After infecting VeroE6/TMPRSS2 cells with SARS-CoV-2, lysates of the Kampo formulas and crude drugs were added, and after 24 h, the infectious titer in the medium was measured by the TCID 50 method. Maoto was the most effective among the Kampo formulas, and Ephedrae herba was the most effective among the constituent crude drugs. However, a comparison of the suppressive effects of Ephedrae herba and Kampo formulas containing Ephedrae herba showed that the suppressive effect on virus infection did not depend on the content of Ephedrae herba. Based on the results, we believe that the use of Maoto among Kampo formulas is suitable as a countermeasure against COVID-19., 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 Kakimoto, Nomura, Nazmul, Kitagawa, Kanno, Ogawa-Ochiai, Ohge, Ito and Sakaguchi.)

In this study, we verified the effectiveness of Kampo medicine by evaluating the changes in the feature values of facial skin texture and microcirculation at two distinct tissue depths (subcutaneous 2 mm and 8 mm). A total of 80 patients who took the Kampo formula participated in this study, and the changes in the feature values of facial skin texture and microcirculation were measured before and after Kampo treatment. The treatment period lasted 6-18 months, according to the doctor's judgment. The total area of the sulci cutis and the average thickness of the sulci cutis significantly decreased ( P  < 0.05), and the pixels of the grayscale image increased after Kampo treatment ( P  < 0.05). Moreover, the blood flow velocity at 8 mm depth significantly increased after Kampo treatment ( P  < 0.05). In this study, we specifically noted changes in the skin texture and microcirculation after Kampo treatment., (© International Society of Artificial Life and Robotics (ISAROB) 2022.)

We developed a system to improve the quality of telemedicine, and the test results obtained have been presented in this paper, along with the technical details of the system. The spread of COVID-19 has accelerated the need for telemedicine to effectively prevent infections. However, in traditional Japanese medicine (Kampo), where color is essential, an accurate diagnosis cannot be made without color reproduction. Because commercial smartphones cannot reproduce colors with the level of fidelity required for medical treatments, we created a color chart that includes the human skin and tongue colors to help doctors identify their colors accurately during a telemedicine examination. Further, we developed a telemedicine system that allows for automatic color correction using a mobile device, with a color chart and non-contact heart rate measurements., (© International Society of Artificial Life and Robotics (ISAROB) 2022.)

Abstract: Lymphatic malformations (LMs) are congenital malformations of the lymphatic system that cause considerable cosmetic and functional complications. In this study, we present 8 children with LM who were treated with the Kampo medicine eppikajutsuto (EKJT).Between 2001 and 2020, 8 children (male: 4, female: 4) with LMs who underwent magnetic resonance imaging (MRI) evaluation both before and after treatment or observation were selected for investigating the effect of EKJT. Two patients were observed without any treatment for 24 and 60 months. EKJT was evaluated based on percentage reduction, defined as the percentage of total lesions that decreased in size, confirmed by radiological examination after initiating treatment with EKJT or determined by observation alone. Volumetric analysis of LMs on MRI was performed using the Digital Imaging and Communications in Medicine viewer.Six patients were treated with EKJT. The mean observational period was 13.2 months (range: 6-24 months). The mean reduction in LM volume on MRI was 73.0% in treated patients and -66.3% in observed patients. Two of the 6 lesions exhibited complete reduction, 2 exhibited marked (>90%) reduction, 1 exhibited moderate reduction, and 1 exhibited a small response. The treatment was well-tolerated, with no severe adverse events.This preliminary study demonstrated the beneficial effects of EKJT. Prospective evaluations of this promising therapeutic modality are warranted based on the results of this study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Amid the global outbreak of coronavirus disease 2019 (COVID-19), it may be expected that low-toxicity natural compounds, such as Kampo formulas, will have a preventive effect on COVID-19. Although the biological properties and safety of the representative Kampo compounds, hochuekkito (HET) and kakkonto (KKT), have been confirmed in various animal model experiments, clinical studies, and a few human studies to induce biological effects on various infectious diseases without significant toxicity, it is unclear whether HET and KKT are safe and effective for COVID-19 prevention. The study population included healthcare workers (HCWs), as they are at a higher risk of infection than the other populations. We retrospectively investigated the immunological and preventive effects of HET and KTT against COVID-19. We included 27 HCWs (aged 21-72 years, F:M = 18:9) from hospitals and clinics of the Hokuriku-Tokai region. The HCWs received HET and KKT for general fatigue and myalgia during this period for 28 days. We obtained patient clinical data from electronic medical records. We analyzed the changes in immunomodulation before and after the administration of the formulas from residual specimens based on the expression of relevant surface markers. The specimens were also tested for the presence of antibodies against severe acute respiratory syndrome coronavirus 2. The following side effects were reported: abdominal discomfort in five patients, diarrhea in two, and loose or soft stool in three. All 27 HCWs tested negative for COVID-19 antibodies. HET and KKT administration significantly increased the absolute number of circulating lymphocytes expressing the activating receptors NKp46, NKp30, and suppressing receptor NKG2A. There was also a significant increase in the absolute number of circulating lymphocytes expressing the receptors TLR4, OX40, 4-1BB, GITR, PD-1, and ICOS. These data indicate that HET and KKT can enhance and modulate NK activity in circulating human immune cells. The immunomodulatory effects, such as activation and regulation of T cells, are consistent with a putative improvement in infectious immunosurveillance. An increase in the number of T cells and CD4/CD8-positive cells indicates an enhanced ability to protect against infection. HET and KKT may prevent the onset or worsening of COVID-19 through their immunomodulatory effects., 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 © 2021 Ogawa-Ochiai, Ishikawa, Li, Vu Quang, Kimoto, Takamura, Hongawa, Hane, Suzuki, Okajima, Mori, Ito and Takami.)

The circumference of a limb is an important parameter in the follow-up of an edema. Recently, several methods of measuring the circumference on a limb using 3D cameras have been proposed. However, the 3D cameras used are expensive and difficult to implement in general medical facilities. In this study, we propose a circumference-measurement method using a Structure Sensor. First, the leg is photographed and unnecessary background objects are removed from the obtained point cloud. Next, a cross-sectional view is obtained by slicing the point cloud at the specified leg height. Finally, the circumference measurement at a specified leg height is performed by calculating the circumference using the acquired cross-sectional view. Using this method, the leg circumferences of two healthy subjects were measured at two points. For comparison, circumferences were also measured with a measuring tape. The difference between the values estimated using our method and the measured values was generally less than 0.5 cm.

Liquorice is usually used as crude drug in traditional Japanese Kampo medicine and traditional Chinese medicine. Liquorice-containing glycyrrhizin (GL) can cause pseudohyperaldosteronism as a side effect. Previously, we identified 18 β -glycyrrhetyl-3- O -sulfate ( 3 ) as a GL metabolite in Eisai hyperbilirubinuria rats (EHBRs) with the dysfunction of multidrug resistance-related protein (Mrp2). We speculated that 3 was associated with the onset of liquorice-induced pseudohyperaldosteronism, because it was mainly detected in serum of patients with suspected to have this condition. However, it is predicted that other metabolites might exist in the urine of EHBRs orally treated with glycyrrhetinic acid (GA). We explored other metabolites in the urine of EHBRs, and investigated the pharmacokinetic profiles of the new metabolite in EHBRs and normal Sprague-Dawley rats. We further analyzed the serum concentrations of the new metabolite in the patients of pseudohyperaldosteronism. Finally, we developed the analyzing method of these metabolites as a preventive biomarker for the onset of pseudohyperaldosteronism using an enzyme-linked immunosorbent assay (ELISA). We isolated a new GL metabolite, 18 β -glycyrrhetyl-3- O -sulfate-30- O -glucuronide ( 4 ). Compound 4 significantly inhibited rat type-2 11 β -hydroxysteroid dehydrogenase (11 β -HSD2) and was a substrate of both organic anion transporter (OAT) 1 and OAT3. Compound 4 was also detected in the serum of patients with suspected pseudohyperaldosteronism at an approximately 10-fold lower concentrations than 3 , and these concentrations were positively correlated. Compound 4 showed a lower serum concentration and weaker inhibitory titer on 11 β -HSD2 than 3 . We developed an enzyme-linked immunosorbent assay system using an anti-18 β -glycyrrhetyl-3- O -glucuronide (3MGA) monoclonal antibody to measure the serum concentration of 3 to facilitate the measurement of biomarkers to predict the onset of pseudohyperaldosteronism. Although we found 4 as the secondary candidate causative agent, 3 could be the main potent preventive biomarker of liquorice-induced pseudohyperaldosteronism. Compound 3 was detected in serum at a higher concentration than GA and 4 , implying that 3 may be a pharmacologically active ingredient mediating not only the development of pseudohyperaldosteronism but anti-inflammatory effects in humans administered GL or other liquorice-containing preparations., 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 © 2021 Ishiuchi, Morinaga, Yoshino, Mitamura, Hirasawa, Maki, Tashita, Kondo, Ogawa, Lian, Ogawa-Ochiai, Minamizawa, Namiki, Mimura, Watanabe and Makino.)

Glial cells such as astrocytes and oligodendrocytes play crucial roles in the central nervous system. To investigate the molecular mechanisms underlying the development and the biological functions of glial cells, simple and rapid techniques for glial cell-specific genetic manipulation in the mouse cerebrum would be valuable. Here we uncovered that the Gfa2 promoter is suitable for selective gene expression in astrocytes when used with the piggyBac system and in utero electroporation. In contrast, the Blbp promoter, which has been used to induce astrocyte-specific gene expression in transgenic mice, did not result in astrocyte-specific gene expression. We also identified the Plp1 and Mbp promoters could be used with the piggyBac system and in utero electroporation to induce selective gene expression in oligodendrocytes. Furthermore, using our technique, neuron-astrocyte or neuron-oligodendrocyte interactions can be visualized by labeling neurons, astrocytes and oligodendrocytes differentially. Our study provides a fundamental basis for specific transgene expression in astrocytes and/or oligodendrocytes in the mouse cerebrum.

Background: Colonic diverticular disease has been increasing in prevalence due to the rapidly aging global population, but standard treatment has not changed dramatically in recent years. Daiobotanpito (DBT; Da Huang Mu Dan Tang in Chinese) has been used in medical treatment of acute abdominal abscesses, such as appendicitis or diverticulitis in traditional Japanese (Kampo) medicine for many years, based on more than 3000 years of experience. Prior to this study, a retrospective open-label trial was conducted to compare patients with acute diverticulitis who received oral DBT combined with intravenous antibiotics with those who received intravenous antibiotic alone; it showed a positive effect of DBT on acute diverticulitis. We aim to investigate whether moderate to severe acute diverticulitis shows greater improvement with intravenous antibiotics plus orally administered DBT compared with intravenous antibiotics plus placebo., Methods: This is a two-group, randomized, double-blind, placebo-controlled, multi-center trial, which is designed to evaluate the efficacy and safety of DBT in patients with moderate to severe diverticulitis treated with intravenous antibiotics. Eligible participants will be randomized to either a treatment group receiving a 10-day oral DBT regimen plus conventional therapy or a control group receiving a 10-day placebo regimen plus conventional therapy. The primary outcome will be success in treating diverticulitis: the success rate will be defined as elimination of abdominal pain within 4 days in all patients, and in patients with fever (body temperature ≧ 37.5 °C) on inclusion into this study, fever relief with reduction in body temperature to < 37.5 °C within 3 days. Secondary endpoints will include the number of hospitalization days, changes in inflammatory response (C-reactive protein (CRP), white blood cell (WBC) and neutrophil counts), fever type, number of days before beginning food intake, recurrence rate (observation for 1 year after registration), and adverse event expression rate. Assessments will be performed at baseline and on the day of discharge. The recurrence rate will be recorded at 1 year after registration., Discussion: This study is expected to provide evidence to support the clinical benefits of DBT in the treatment of acute diverticulitis. It may also provide evidence on the efficacy and safety of DBT in the recurrence of acute diverticulitis., Trial Registration: UMIN-CTR: UMIN000027381. Registered on 27 April 2017. https://upload.umin.ac.jp/cgi-bin/ctr/ctr&#95;view&#95;reg.cgi?recptno=R000031377, and changed to jRCTs041180063, registered on 30 July 2019; as a result of the revision of the domestic law in 2018 in Japan.

In this paper, we propose a color reproduction method using color charts to improve the color quality of a telemedicine system. Owing to the spread of COVID-19, the need for telemedicine is rapidly increasing to prevent infections more effectively. However, in practices such as traditional Japanese (Kampo) medicine, where color is used as an important examination factor, an accurate diagnosis cannot be made without adequate color reproduction. In telemedicine using a commercially available smartphone, color reproducibility may deteriorate owing to differences in the devices and lighting, which may result in a misdiagnosis. Therefore, we created a color chart that includes the colors of the human skin and tongue as a tool to help doctors identify the color of patients more accurately when conducting a telemedicine examination. Through a subjective evaluation by eight medical doctors, it was unanimously found that the proposed method is practical in terms of a color examination. The developed color chart can also be used for an automatic color correction., (© International Society of Artificial Life and Robotics (ISAROB) 2020.)

Introduction: Almost all patients with end-of-life cancer experience cancer-related fatigue; however, there are only a few known effective coping methods., Objectives: We will conduct a prospective, multi-center, single-blinded randomized controlled study to evaluate the efficacy of acupuncture for cancer-related fatigue in patients with end-of-life cancer., Methods: We will enroll 120 patients with cancer hospitalized in a palliative care unit or receiving consultation from a palliative care team in four hospitals. We will add acupuncture treatment; specifically, contact needle therapy (CNT), consisting of an intervention per week period to the usual care. The primary outcome measure will be the Cancer Fatigue Scale (CFS) score while the secondary outcome measures will be the Numerical Rating Scale (NRS) score for fatigue, pain, and salivary amylase levels., Conclusion: We will evaluate the possibility of using acupuncture therapy, that is, CNT, in relieving fatigue sensation in patients with advanced cancer., Trial Registration: UMIN000028304, registered on July 21st, 2017; https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000032401.

Liquorice [main ingredient, glycyrrhizin (GL)] is widely used as a food sweetener and herbal medicine. Occasionally, liquorice consumption causes pseudoaldosteronism as a side effect which causes oedema, hypokalaemia, and hypertension due to hyperactivity of mineral corticoid receptor. We aimed to detect GL metabolites in human blood and urine samples and to determine the pathological relationship between GL metabolites and pseudoaldosteronism. For this multi-centre, retrospective, cross-sectional study, we recruited patients who had visited Center for Kampo Medicine in Keio University Hospital, Department of Japanese Oriental (Kampo) Medicine in Chiba University Hospital, Clinic of Japanese Oriental (Kampo) Medicine in Kanazawa University Hospital, and Department of Oriental Medicine in Kameda Medical Center from November 2011 to July 2018. We collected laboratory data including concentration of serum potassium, plasma activity of renin and aldosterone, and residual blood and/or urine samples of participants who had experienced symptoms/signs of pseudoaldosteronism in the form of increase in blood pressure and occurrence or aggregation of oedema while taking liquorice-containing herbal preparations, and measured GL metabolites using a highly selective liquid chromatography tandem mass spectrometer system. We registered 97 participants (mean age 60 ± 15 years; male:female 14:83). 18β-glycyrrhetinic acid (GA) was detected in 67 serum samples (median 122 nM, range 5 nM-1.8 µM) and 18β-glycyrrhetyl-3-O-sulfate (compound 3) in 68 samples (median 239 nM, range 2 nM-4.2 µM). 3-Monoglucuronyl 18β-glycyrrhetinic acid, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate-30-glucuronide, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate, and GL itself were not or rarely detected. We could not find any correlation between blood pressure or peripheral oedema and serum concentration of GL metabolites. Sulfotransferase 2A1 catalysed the metabolic reaction of GA to compound 3, a major GL metabolite in human blood. High serum concentration of compound 3 was related to lower renin, aldosterone, and potassium levels, suggesting a pathological relationship between compound 3 and liquorice-induced pseudoaldosteronism. This is the first study to identify the association between a novel metabolite, compound 3, and the incidence of pseudoaldosteronism, highlighting it as a promising biomarker.

This review aims to understand the clinical efficacy of Panax ginseng (PG) for managing frailty-related disorders by reviewing meta-analyses, systematic reviews, and randomized clinical trial data. PG is widely used in traditional medicine, mainly in East Asia. It has traditionally been indicated for the collapse of qi or for abandoned conditions that manifest as shallow breathing, shortness of breath, cold limbs, profuse sweating, a low pulse rate, or weakness. In accordance with these indications, PG is used for managing conditions such as aging, inflammation, and cancer. PG is also used in some functional foods or supplements. Some studies have shown the effects of ginsenosides, which are the major constituents of PG. With regard to pharmacological activities of ginseng saponins, it has been presumed that these ginsenosides are metabolized into active forms by human intestinal microbiota after being taken orally. Therefore, we focused on reviewing the data of clinical studies on PG. Although there has been no study that directly investigated the effect of PG on frailty, a number of clinical studies have been conducted to investigate the efficacy and safety of PG and its interactions with other modern ginseng medications and ginseng-containing formulas. We searched the randomized controlled trial data from 1995 to 2018 and reviewed the potential effects of PG on frailty-related disorders. We reviewed the effects of PG on glucose metabolism, fatigue, hypertension, cardiovascular disorders, chronic obstructive pulmonary disease, renal function, cognitive function, and immune function. Our review showed some evidence for the usefulness of ginseng, which suggests that it has the potential to be used for the management of aging-related and frailty symptoms, such as fatigue and hypertension. The main limitation of this review is that no study has directly investigated the effect of PG on frailty. Instead we investigated frailty-related disorders, and the limitations of the available studies were small sample sizes and a poor methodological quality; besides, only a few studies targeted elderly people, and few included placebo controls. Larger, well-designed studies are needed to determine the effect of PG on frailty in the future.

Objective: To present the efficacy of Japanese-traditional medicine (Kampo) for a case with vascular malformation., Methods: A case study and literature review., Patient: A 62-year-old female presented with dysphagia and spitting blood. Esophagogastroduodenoscopy showed a longitudinal lobulated and septated mass in the posterior pharynx. On MR imaging, the mass showed hyperintensity on T2-weighted images and heterogeneous enhancement on Gadlinium-enhanced T1-weighted images, suggestive of a low-flow vascular malformation., Intervention: According to the Kampo diagnosis, kamisyouyousan and ninjinyoueito were prescribed to this patient. The effect of Kampo medicine was evaluated with improvement of her symptoms and volumetry of MRI findings., Result: The longitudinal pharyngeal mass was markedly decreased and her symptoms disappeared after 2 years of Kampo administration., Conclusions: Kampo medicine can be a novel alternative therapy for VM., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Conventional 3-dimensional color spaces such as L*a*b* or L*C*h have a limitation in that colors of materials can only be separated on the same hyperplane. Therefore, it would be useful to find appropriate axes for dental color analysis by analyzing spectral data itself, rather than conventional 3-dimensional color spaces., Methods: Hyperspectral data are detailed color spectra with narrow spectral bands over a continuous spectral range. We acquired hyperspectral data of the shade guides without specular reflection, and standardized them as reflectance data. Then, reflectance data were weighed by luminous efficiency function, and used in principal component analysis (PCA). Principal components (PCs) and their contribution, and values of respective shades to respective PCs were calculated as PC scores., Results: Cumulate contribution rate of 1st to 3rd PCs were approximately 100%, which meant shade colors were very similar to each other. Respective PCs showed specific figures, and values of shades showed sequences unique to each PC, which were independent of each other; values to the 1st PC showed gradual changes with change in shade numbering, values to the 2nd PC showed relatively high scores on opaque shades, values to the 4th PC showed lower scores on B and C group shades, and values to the 6th PC showed differences between manufacturers., Significance: Using PCA, we could find axes independent of the conventional 3-dimensional color spaces. These axes reflected certain changes which are not detected on conventional color spaces. Our methods are taking into account color matching under any illumination by focusing on the spectra themselves, and we can discuss about components of the teeth from spectra of resulting principal components. By applying our method to conventional systems, it would help diagnose color differences of dental materials., (Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.)

Background: In Kampo medicine (Japanese traditional herbal medicine), the appearance of the tongue contains a lot of useful information for diagnosis. However, an inspection of the tongue is not considered to be important in modern medical diagnosis, since the skills applied in the examination are difficult to understand. Thus, we developed an imaging system and algorithm for quantitative analysis of the tongue to provide the traditional techniques of Kampo with greater objectivity., Materials and Methods: Tongue images were taken from 9 healthy subjects for 3 consecutive weeks (5 days/week), 12 times a day, with 300 images taken successively within 30 s each time. Then, the temporal color changes in 30 s, 1 day, and 3 weeks were measured in the device-independent International Commission on Illumination (CIE) 1976 L*a*b* color space., Results: The tongue color change in 30 s varied between individuals, and it was mainly classified into 3 patterns. This image acquisition system and valid color management should help all tongue-related research, and the 30-s temporal color change might be an important target for further tongue analysis., Conclusions: We were able to acquire tongue images without specular reflection and with valid color reproduction, and the color change in 30 s was found to vary. Tongue color changes have not been mentioned in the classics of Kampo medicine, since they were certainly impossible to discriminate by the naked eye. The change during 30 s is a new finding based on the electronic devices, and together they are expected to become a new criterion for tongue analysis., (Copyright © 2012 S. Karger AG, Basel.)

Objective: The authors report a case of mediastinal lymphangioma successfully treated with Kampo medicine., Methods: A 2-year-old boy with an axillary soft mass consulted our clinic. Physical examination findings were normal except for axillary elastic swelling. The neck and chest magnetic resonance imaging scan (MRI) showed a multilocular mass starting from a cervical lesion and extending above the carina., Results: After 9 months of Kampo administration, MRI showed marked regression of mediastinal lymphangioma., Conclusions: It was found that Kampo medicine might be safe and effective as an alternative choice of treatment for lymphangiomas.

Purpose: Kampo medicine (Japanese traditional herbal medicine) contains concepts useful for preventive medicine. For example, "Mibyou" (disease-oriented state) aims to prevent illness by early recognition. Kampo diagnosis is based on subjective examinations, such as tongue inspection, by trained specialist physicians. An objective metric of the tongue color spectrum was developed as a surrogate for subjective visual inspection., Methods: Tongue images were acquired with a hyperspectral imaging system, and the uncoated tongue region was segmented automatically. The spectral information of the uncoated tongue area was analyzed by principal component analysis (PCA). The component vector most representative of each clinical symptom was found by rotating the vector on a plane spanned by two arbitrary principal component vectors., Results: The system was tested in human volunteers. Forty-four hyperspectral images were acquired from 30 healthy male subjects for initial testing. The Oketsu (blood stagnation) score was determined by an experienced clinician in Kampo medicine from 27 of 30 subjects. The correlation between respective principal components and Oketsu score was 0.67 at maximum, and increased to 0.73 by linear combination, while it was -0.75 by vector rotation. Significant correlations for many disorders were demonstrated, and vector rotation showed better correlation than linear combination., Conclusions: A PCA-based algorithm was developed to objectively evaluate patients using color images of the tongue surface. Testing showed that this method was a feasible surrogate for expert visual tongue analysis. This tool should help non-trained people identify "Mibyou" health status for individuals. The algorithm is free of empirical criteria, and it may be it applicable to many hyperspectral image types.

In this article, we propose an effective colorprocessing algorithm to analyze the hyperspectral image of the tongue and its application to preventive medicine by the concept of Japanese traditional herbal medicine (Kampo medicine). Kampo medicine contains a number of concepts useful for preventive medicine such as "Mibyou" - disease-oriented state - signs of abnormalities. Hyperspectral images of the tongue were taken with the system with an integrating sphere, and tongue area without coating was eliminated automatically. Then, spectral information of the tongue area without coating was analyzed by principal component analysis, and the component vector best representing the clinical symptom was found by rotating the vector on a plane spanned by two arbitrary principal component vectors.