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This study aims to develop guidelines of key concepts and specific considerations to make the research more ethical when conducting neurological examinations and treatment interventions in mentally ill patients. We analyzed guideline development theory and literature, previous issues, and discussions with specialists of philosophy, medicine, sociology, and bioethics. The selection of research participants, drafting of intervention plans, and informed consent process were examined with reference to the dual burden; the minimal risk as a general rule of ethical allowance levels, assent and dissent to assess the individual's judgment capacity for consent, relational autonomy for personal consent with assistance by the proxy, and risk/benefit assessments. When conducting studies, this guideline requires that these three processes be set up appropriately on a case-by-case basis., Supplementary Information: The online version contains supplementary material available at 10.1007/s41649-023-00240-x., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2023.)

Background/aim: Itraconazole (ITZ), an antifungal agent, has been reported to have anti-tumor effects in patients with multiple cancer types. We investigated the involvement of tumor-associated macrophages (TAMs) in its tumor-agnostic mechanism., Materials and Methods: M1 and M2 macrophages were established from human monocyte leukemia cell line (THP-1) and their phenotypes were determined morphologically. Cell membrane antigens and secreted proteins were evaluated by western blots and enzyme-linked immunosorbent assay, respectively. The proteomic profiling of cells was done by liquid chromatography with tandem mass spectrometry and analyzed. Viability of cervical cancer cells (CaSki) was evaluated after addition of the supernatant of M2 macrophages and during co-culture with M2 macrophages, with or without 10 -5 M ITZ., Results: Co-culture of M1 macrophages inhibited the proliferation of CaSki cells (p=0.012), while that of M2 macrophages promoted their proliferation (p<0.0001). After treatment of M2 macrophages with ITZ for 24 h, they changed into M1-like shape with decreased expression of cluster of differentiation 163 (CD163) and chemokine ligand 18 (CCL18). The M1-like shape was maintained for 7 weeks of ITZ treatment and reverted to original after ITZ removal. Proteomic analysis of ITZ treated-M2 macrophages also demonstrated M1-like signature including the elevated levels of tumor necrosis factor (TNF)-related proteins. After treatment with ITZ, both the supernatant of the M2 macrophages and the co-culture with M2 macrophages significantly inhibited the proliferation of CaSki cells (each, p<0.0001)., Conclusion: ITZ repolarized M2 macrophages to M1 type and suppressed cervical cancer cell growth demonstrating TAM-mediated anti-cancer activity of ITZ., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We applied a combination of compressed-sensing (CS) and retrospective motion correction to free-breathing cine magnetic resonance (MR) (FBCS cine MoCo). We validated FBCS cine MoCo by comparing it with breath-hold (BH) conventional cine MR., Materials and Methods: Thirty-five volunteers underwent both FBCS cine MoCo and BH conventional cine MR imaging. Twelve consecutive short-axis cine images were obtained. We compared the examination time, image quality and biventricular volumetric assessments between the two cine MR., Results: FBCS cine MoCo required a significantly shorter examination time than BH conventional cine (135 s [110-143 s] vs. 198 s [186-349 s], p < 0.001). The image quality scores were not significantly different between the two techniques (End-diastole: FBCS cine MoCo; 4.7 ± 0.5 vs. BH conventional cine; 4.6 ± 0.6; p = 0.77, End-systole: FBCS cine MoCo; 4.5 ± 0.5 vs. BH conventional cine; 4.5 ± 0.6; p = 0.52). No significant differences were observed in all biventricular volumetric assessments between the two techniques. The mean differences with 95% confidence interval (CI), based on Bland-Altman analysis, were - 0.3 mL (- 8.2 - 7.5 mL) for LVEDV, 0.2 mL (- 5.6 - 5.9 mL) for LVESV, - 0.5 mL (- 6.3 - 5.2 mL) for LVSV, - 0.3% (- 3.5 - 3.0%) for LVEF, - 0.1 g (- 8.5 - 8.3 g) for LVED mass, 1.4 mL (- 15.5 - 18.3 mL) for RVEDV, 2.1 mL (- 11.2 - 15.3 mL) for RVESV, - 0.6 mL (- 9.7 - 8.4 mL) for RVSV, - 1.0% (- 6.5 - 4.6%) for RVEF., Conclusion: FBCS cine MoCo can potentially replace multiple BH conventional cine MR and improve the clinical utility of cine MR., (© 2022. The Author(s).)

Background: In current Western medical ethics, patient-centered medicine is considered the norm. However, the cultural background of collectivism in East Asia often leads to family-centered decision-making. In Japan, prior studies have reported that family-centered decision-making is more likely to be preferred in situations of disease notification and end-of-life decision-making. Nonetheless, there has been a recent shift from collectivism to individualism due to changes in the social structure. Various personal factors have also been reported to influence moral decision-making. Therefore, this study examined whether the current trend in attitudes of healthcare decision-making in Japan is family-centered or patient-centered among the general public and physicians. In addition, the personal factors that influence this tendency were examined., Methods: Three vignettes on disease notification and two vignettes on decision-making during end-of-life care were created, and 457 members of the public and 284 physicians were asked about their attitudes (behavioral intentions) regarding these vignettes., Results: Approximately, 95% of physicians were patient-centered in explaining the patient's severe medical condition. However, approximately 80% of physicians emphasized the wishes of the family over patient wishes when making life-sustaining decisions. Nearly half the general public emphasized the patient's wishes in the explanation of a severe medical condition and in life-sustaining decisions. In both the public and physician groups, personal factors, particularly the presence or absence of a disease under treatment and prior caregiving experience, influenced ethical attitudes toward medical treatment decisions., Conclusions: In relatively low-conflict situations, such as the announcement of a patient's medical condition, physicians tended to be patient-centered, while they tended to be family-centered in situations of strong conflict in withholding life-sustaining treatment. The fact that personal factors influenced the family-centered response in situations of strong conflict highlights the importance of not only acquiring knowledge of medical ethics but also learning to fairly apply this knowledge in practice.

The main objective of this study was to investigate the cause of gel fouling in membrane bioreactors (MBRs) treating real sewage in terms of soluble microbial products (SMPs) and microbial aspects. Two anoxic/oxic-MBRs were operated as the control reactor (S1) and the sludge loading rate increased reactor (S2). The reactors were operated under low-temperature around 11 °C conditions. Membrane permeability substantially decreased in S2, and gel layer biofilm was formed on membrane surface. In contrast, the permeability of S1 gradually decreased and cake layer formed. When gel fouling occurred, the protein and polysaccharide of SMP in S2 were 47 and 23 mg L -1 , which were significantly lower than those recorded in S1 accounted for 118 and 68 mg L -1 , respectively. Furthermore, the total organic carbon concentration of SMPs was 24 mg L -1 , which was lower than the influent in S2, accounted for 62 mg L -1 . Finally, Campylobacteraceae which exists in sewage and uncultured OD1, dominated the gel layer biofilm in S2, unlike the cake layer biofilm in S1. These results indicated that the gel layer biofilm might be composed of influent substances, demonstrating the importance of influent decomposition in MBR for gel fouling mitigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background/purpose: The aim of this study is to clarify the relation between the incision size for endoscopic sphincterotomy (EST) and common bile duct stone (CBDS) recurrence., Methods: Patients who underwent elective endoscopic treatment for CBDS between January 2013 and December 2017 were enrolled, excluding those who met the exclusion criteria. The clinical characteristics were investigated using propensity score matching analysis., Results: A total of 243 patients were investigated. Propensity scores were calculated using multinomial logistic regression with five relevant variables (age, gender, follow-up time, maximum stone size, and bile duct diameter), which led to extraction of 188 cases to compose cohorts of the small and medium EST incision groups. The CBDS recurrence rate was 17.0% in the small incision group and 6.4% in the medium incision group. Multivariate analysis identified the medium incision as an independent predictor of CBDS recurrence (hazard ratio 0.350, 95% confidence interval 0.133-0.922, P = .034). The CBDS non-recurrence rate of the medium incision group was significantly higher than that of the small incision group (log-rank test P = .019)., Conclusions: Our findings suggest that the CBDS recurrence rate was lower in EST with medium incision size than with small incision size., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Clinical ethics consultation (CEC) is not sufficiently widespread in Japan. A possible reason is that a practical training system for CEC has not been established. Hence, we have developed "immersive role-play (IR)" as a practical training program that applies a new theatrical technique, immersive theater, to role-play learning. Its characteristics include high fidelity in the use of a studio and actors and dynamic realism in the progression of the scenario to immerse learners in role-play learning., Methods: We offered an intensive course on CEC for healthcare professionals from 2016 to 2019, with IR as part of the course curriculum. A questionnaire survey was administered to the participants regarding the educational effectiveness of IR. The questionnaire was anonymous, and participants responded on a 4-point Likert scale regarding their satisfaction with IR and their perception of its learning effects. An open-ended section at the end of the questionnaire asked about the effectiveness and areas for improvement of IR., Results: The questionnaire survey showed good results in all categories: usefulness, satisfaction, understanding, and interest. In the questions that compared the learning to traditional role-play learning, the participants gave significantly high ratings, specifically for "realism," "seriousness," "understanding the importance of communication skills," and "understanding the diversity of the narratives." In the free-text responses, the most frequent response was that they learned a lot about the practical procedures for participation., Conclusion: IR is sufficiently effective as a practical educational program, but not for everyone. It is suitable for those who are or will soon work as consultants. Conversely, beginners and intermediates who have not fully mastered the CEC theory and skills will need a stage-specific educational program separate from the IR., (© 2022. The Author(s).)

Background: When a patient with anorexia nervosa refuses treatment despite a physically critical condition, the therapist considers involuntary inpatient treatment under the Mental Health Law. However, ethical and practical problems arise from its application. In this study, a survey of treatment providers for eating disorders and psychiatric review board members was conducted regarding indications for involuntary hospitalization under the Mental Health Act for refusal of treatment for anorexia nervosa., Methods: A survey of 212 physicians affiliated with the Japanese Society for Eating Disorders and 180 members of Mental Health Care Review Boards across Japan was conducted using six vignette cases of patients with anorexia nervosa refusing treatment., Results: Regardless of the duration of illness or age of the patient, few physicians chose compulsory hospitalization with or without the consent of the family, while the largest number of physicians chose hospitalization for medical care and protection when there was family consent. Among committee members, only hospitalization for medical care and protection was determined to be appropriate when there was family consent. Both hospitalization for medical care and protection, and compulsory hospitalization were deemed appropriate in the absence of family consent. Committee members who adjudged refusal of treatment for anorexia nervosa as self-injurious behavior suggested that compulsory hospitalization was indicated., Conclusions: When a patient with life-threatening anorexia nervosa refuses inpatient treatment, hospitalization for medical care and protection is actively chosen if the patient's family consents. Mental Health Care Review Board members considered this acceptable. However, if the family does not consent, the physicians did not choose compulsory hospitalization, and the psychiatric review board was divided on this. Consensus was not achieved in this regard., (© 2022. The Author(s).)

Background: Medical institutions are required to report suspected cases of child abuse to administrative agencies, such as child guidance centers in Japan. It is left to the discretion of the medical institutions whether to notify the family of the child or the center. However, it is unclear what kinds of measures are being taken to ensure a robust policy of notification versus non-notification and how notifying the family will affect the child., Methods: An unregistered questionnaire survey on reporting suspected child abuse cases to child consultation centers and notifying families was conducted by mail across 518 pediatric specialist training facility hospitals designated by the Japanese Pediatric Society., Results: Responses were received from 323 facilities (62.4% response rate), of which 5 facilities were excluded because of incomplete responses. Therefore, in all, 318 facilities were included in the analysis. The results showed that 59.8% of the facilities had a policy of notifying the family, 33.7% said the decision varies from case to case, and 6.6% did not have a policy of notifying the family. The facilities that had a policy of either notifying or not notifying the family were less likely to experience problems than those with a policy of deciding on a case-by-case basis. The proportion of cases in which some problems occurred was higher in the cases where families were notified than in the cases where they were not, with 51.4% of the children experiencing worsening of relationships with family members. In the cases where the families were not notified, the children were twice as likely to experience further abuse than in cases where the families were notified., Conclusion: Problems arise in the case of both notification and non-notification. It is necessary to examine background factors and specific methods of notification in the cases where problems arise.

Aim: To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a pathological complete response (pCR) after the completion of NAC., Materials and Methods: This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density [PD] and their standard deviations [SD]) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR., Results: Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively., Conclusions: The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

In mechanochromic material research, a serious problem is that mechanical treatment cannot be applied to the materials because of their responsiveness to stimuli. Inkjet printing is a useful solution deposition method for electronics, but materials must be processed to be suitable for an inkjet printer. Fluorenylidene-acridane (FA) exhibits ground-state mechanochromism with visual color changes and responds not only to mechanical pressure but also to alcohol. Alcohol inhibits the color change induced by mechanical stimulation because the mechanochromism of FA is based on a conformational change in its molecular structure. This phenomenon suggests that the mechanochromism of FA can be controlled using alcohol. For use in inkjet printing, minute particles of FA obtained by bead milling in ethanol were investigated for uniformity and size by scanning electron microscopy and gas adsorption measurement. Also, ink containing FA particles was prepared and examined for physical properties such as viscosity and surface tension. It was confirmed that the inkjet-printed pattern demonstrated visual color changes between yellow and green in response to mechanical pressure and alcohol. This report describing the control of mechanochromism and its specific application is expected to contribute to broadening the mechanochromic materials research field., (© 2022. The Author(s).)

Hospital ethics committees (HECs) are expected to play extremely broad and pivotal roles such as case consultation, education of staffs on healthcare ethics, and institutional policy formation. Despite the growing importance of HECs, there are no standards for setup and operation of HECs, and composition and activities of HECs at each institution are rarely disclosed in Japan. In addition, there is also a lack of information sharing and collaboration among HECs. Therefore, the authors established the Consortium of Hospital Ethics Committees (CHEC) in October 2020, which has been regularly hosting a couple of core activities. One is the Healthcare Ethics Forum, held monthly online for CHEC members to freely discuss HECs and healthcare ethics consultation. The other is the Collaboration Conference of Hospital Ethics Committees, intended to provide a place for HEC members and administrative officers from across Japan to exchange information of their HECs, learn from each other, and cooperate to operate HECs appropriately. In this paper, the authors introduced CHEC as well as reported the results of a questionnaire survey conducted at the first conference among participating facilities, suggesting the diverse structures and activities of HECs in Japan., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© National University of Singapore and Springer Nature Singapore Pte Ltd. 2022.)

Background: There are several psychosocial and ethical issues surrounding the decision making of living kidney transplant donors. This study aimed to determine what health care professionals (HPs) consider in their clinical practice and their attitudes toward donors' decision-making processes., Methods: Face-to-face semistructured interviews were conducted with 15 HPs. A thematic analysis was performed to categorize the thematic elements of the transcripts. All procedures were approved by the relevant review board and conducted in accordance with the Declaration of Helsinki., Results: Six main categories-maintaining family relationships, improving donor understanding, supporting voluntary decision making, setting the environment for the examination, having different attitudes toward the donor's intentions, and resisting confirmation of intent-were identified. The HPs provided diverse considerations to respect the donors' autonomy., Conclusion: In clinical practice, there is a lack of practical methods to confirm living donors' levels of understanding and spontaneity, suggesting that these methods need to be established. Factors related to family functioning may reflect the unique culture of Japan, and this may be indicative of the need to consider treatment based on cultural values., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: With a recent increase in the prevalence of autism spectrum disorder (ASD), an important issue has emerged in clinical practice regarding when and how patients themselves should be given explanations following a diagnosis of ASD. The clinical guidelines of the UK National Institute for Health and Care Excellence state that children diagnosed with ASD should receive an explanation about what ASD is and how it affects their development and functioning-"if appropriate". However, the guidelines do not provide any specifics regarding what constitutes "appropriate" situations METHODS: We conducted an anonymous self-administered postal questionnaire survey targeting all members of the Japanese Society for Child and Adolescent Psychiatry (n=1,995). The analysis included only physicians who had newly diagnosed pediatric patients with ASD in the past year. We imposed a limit of one year because diagnoses further back than that are difficult to recall; in other words, this would enhance the recall bias RESULTS: The recovery rate was 30.8%, and the rate of diagnosis disclosure to patients themselves without intellectual disability was 15.3%. We asked 361 physicians who responded that "deciding on a case-by-case basis" was the ideal way to disclose an ASD diagnosis about 20 items prioritized by physicians at the time of diagnosis disclosure and extracted three factors through exploratory factor analysis. Multiple logistic regression analysis was performed with physician attributes, awareness of ASD as a disorder or personality, and the three extracted factors as explanatory variables; diagnosis disclosure was the dependent variable. The patient age group and only one of the three factors (i.e., "factor related to readiness to accept diagnosis") showed a significant association with disclosure of the diagnosis to the individual. Items included in the "factor related to readiness to accept diagnosis" were as follows: the degree of parental understanding, relationship of the patient with their parents/physician, agreement in opinion between parents, parental consent, "sufficient" patient understanding, symptom stabilization, and a guarantee of sufficient time required to explain the diagnosis to the patient CONCLUSION: In clinical settings, disclosing an ASD diagnosis with the consideration of patient/parent readiness toward accepting the diagnosis could help to guide physicians in determining an ideal timing for disclosure. Future studies are needed to establish detailed and concrete guidelines regarding disclosure of an ASD diagnosis to patients., (© 2022. The Author(s).)

Background: Patients with anorexia nervosa (AN) often refuse treatment despite their extremely low nutritional status. This study investigated the methods of assessing the mental capacity of patients with anorexia nervosa (AN) who refuse treatment by physicians in Japan, the United Kingdom (UK), and the United States (USA). It also identified the key points of the assessment., Methods: A questionnaire survey using a case vignette was conducted among physicians (Japan, n = 53; UK, n = 85; USA, n = 85) who treat eating disorders., Results: A total of 23% of physicians in Japan, 32% in the UK, and 35% in the USA reported that they believe patients with AN lack the capacity to make appropriate decisions. Physicians who considered patients with AN to have an impaired mental capacity placed significantly more emphasis on the level of psychopathological values, which are values caused by AN (and can be changed by recovery) that affect the ability to be rational, when assessing the mental capacity of these patients. Conversely, physicians who considered patients with AN to have full mental capacity placed significantly more weight on the ability to express a choice or preference., Conclusions: It may be necessary to add the level of psychopathological values to the assessment of the mental capacity in relation to obesity fears and emotional disturbances of Patients with AN because emotions caused by psychopathological values strongly influence decision-making. By considering the level of psychopathological values, it may be feasible to reflect the actual situation during the assessment of the mental capacity of those who refuse AN treatment, thus making it more likely to overcome ethical dilemmas., (© 2022. The Author(s).)

Photodynamic therapy is useful as organ-preservation salvage therapy for residual recurrence of esophageal squamous cell carcinoma after chemoradiation therapy. However, the high residual recurrence rate of photodynamic therapy poses a problem. We herein report a patient who underwent photodynamic therapy for recurrence of superficial esophageal squamous cell carcinoma after chemoradiation therapy. The patient later exhibited another episode of recurrence of superficial esophageal squamous cell carcinoma, and R0 curative resection was obtained with endoscopic submucosal dissection. This suggests that endoscopic submucosal dissection may be an effective treatment option that can achieve R0 resection even for residual superficial cancer after salvage photodynamic therapy.

Background: This study investigated the attitudes of physicians in Japan, the United Kingdom (UK), and the United States (US) toward refusal of treatment for anorexia nervosa., Methods: A questionnaire survey was administered to physicians treating patients with eating disorder (Japan, n = 55; UK, n = 84; US, n = 82) to evaluate their treatment strategies for fictitious cases of refusal of treatment for anorexia nervosa., Results: For acute patients, 53 (96.3%) physicians in Japan, 65 (77.4%) in the UK, and 54 (65.9%) in the US chose compulsory treatment if the patient's family requested treatment, while 46 (83.6%) physicians in Japan, 53 (63.1%) in the UK, and 47 (57.3%) in the US chose compulsory treatment if the family left the decision to the patient. For severe and enduring anorexia nervosa, 53 (96.3%) physicians in Japan, 62 (73.8%) in the UK, and 57 (69.5%) in the US chose compulsory treatment if the patient's family requested treatment, while 38 (69.1%) physicians in Japan, 56 (66.7%) in the UK, and 55 (67.1%) in the US chose compulsory treatment if the family left the decision to the patient., Conclusions: Physicians in all three countries tended to choose compulsory treatment irrespective of disease duration or whether the patient's family requested treatment or not. This may indicate that medical practitioners value the ethical obligation of beneficence, giving priority to the protection of life. Attitudes toward refusal of treatment during a life crisis tend to vary among medical professionals, particularly if the patient's family does not request treatment., (© 2022. The Author(s).)

No standard chemotherapy is available after disease progression or anaphylaxis during platinum chemotherapy among patients with recurrent cervical cancer. Here we report the efficacy and toxicities of metronomic chemotherapy consisting of 50 mg of oral cyclophosphamide (CPA) daily and intravenous 15 mg/kg of bevacizumab (BEV) repeated every 3 weeks (CPA-BEV). Treated patients were retrospectively reviewed. Adverse events and response rates were recorded according to the Common Toxicity Criteria for Adverse Events (CTCAE) ver 5.0 and Response Evaluation Criteria In Solid Tumors ver 1.1, respectively. Eleven patients had been treated with CPA-BEV between 2016 and 2021.The pathologic types were squamous cell carcinoma in seven patients, adenocarcinoma in three, and large cell neuroendocrine carcinoma in one. Nine patients had primary concurrent chemoradiotherapy (CCRT). Five patients received more than one prior chemotherapy (excluding CCRT). Six patients had progressive disease during prior platinum-based chemotherapy, four patients recurred within 6 months of the last platinum administration, and one patient had platinum anaphylaxis. Grade 3 or more hematologic toxicities and grade 2 or more non-hematological toxicities were observed in one with grade 3 neutropenia and in one with grade 2 proteinuria, respectively. The median duration of chemotherapy was 2.8 months (range 0.2-30.6 months). One patient had CR but none had PR. Median progression-free survival was 2.8 months (95 %CI: 2.1-10.7 months), and median overall survival was 13.6 months (95 %CI: 8.4-33.7 months). In conclusion, the CPA-BEV regimen showed favorable antitumor activity with minimal toxicity and is promising candidate for second-line chemotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: The purposes of the present study were to describe stroke survivors' experiences and to identify their support needs when faced with decisions about rehabilitation., Methods: Based on the Ottawa Decision Support Framework needs assessment, semi-structured interviews were conducted with 15 stroke survivors. The degree of participation in decision-making and anxiety were assessed quantitatively. All interview transcripts describing their experiences and emotions were qualitatively analyzed., Results: All participants had hemiplegia but could perform their daily activities unassisted. Most participants played an active role in decision-making, but 13 patients felt some anxiety when choosing chronic-phase rehabilitation programs. Qualitative analysis identified 19 codes, of which 13 were categorized into the four factors of knowledge, values, certainty, and support. The codes related to patient feelings of anxiety and insecurity about making decisions were "lack of information about options," difficulty in "selecting appropriate information," and "lack of support" from medical staff. Trustworthy specialist support and prior knowledge of rehabilitation were identified as factors that could help patients feel more secure about making decisions., Conclusions: To support stroke survivors in their decision-making about rehabilitation, each patient should be given a long-term perspective on stroke rehabilitation and sufficient information on rehabilitation options tailored to their individual needs. Decision aids for stroke survivors built on these findings will be used in clinical practice, and their efficacy will be verified in future studies., Competing Interests: CONFLICT OF INTEREST: The authors report no conflicts of interest., (2022 The Japanese Association of Rehabilitation Medicine.)

We herein report a patient with a high bleeding tendency as a result of acquired factor V inhibitor and immune thrombocytopenia (ITP). The administration of prednisolone increased the platelet count, but a fatal bleeding event occurred before platelet levels had sufficiently increased. Factor V is stored in not only plasma but also platelets, and platelet-derived factor V might play a local hemostatic role. Bleeding tendency may be high in rare cases where factor V inhibitor is complicated with severe thrombocytopenia. In such patients, physicians should consider aggressive hemostatic therapy, including plasma exchange, in addition to immunosuppressive therapy.

Cancer cachexia results in the discontinuation of aggressive cancer therapy, and halting its progression has a significant effect on the survival rate and quality of life of patients with cancer. Currently, there are few therapies to control or slow down the progression of cancer cachexia. Although traditional Japanese Kampo medicine is widely used to support aggressive cancer therapy, the relevant scientific evidence is limited. Additionally, Kampo medicines are based on historical experience. In recent years, there have been widespread attempts to prove the efficacy of Kampo medicines through basic research, and an increasing number of studies have clarified the mechanism of action of Kampo medicines at the molecular level. It has been proposed that the improvement of cancer cachexia by Kampo medicines might involve enhancement of feeding via the central nervous system, improvement of protein maintenance in the skeletal muscle, and suppression of inflammatory cytokine production. In particular, among Kampo medicines, tonifying formulae, called "hozai" in Japanese, have been shown to be effective in alleviating cancer cachexia. In this review, we summarize the recent progress of basic and clinical research in Kampo medicines on cancer cachexia, and introduce Kampo medicines that are expected to be attractive supportive cancer medication., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background/aim: Itraconazole shows anticancer activity in various types of cancer but its underlying mechanism is unclear. We investigated the effect of itraconazole on membrane-associated lipids., Materials and Methods: To investigate the influences of itraconazole on cholesterol trafficking, cervical cancer CaSki cells were cultured with itraconazole and analyzed by Filipin staining followed by confocal microscopy. Effect on the glycerophospholipid profiles was analyzed by liquid chromatography/mass spectrometry (LC/MS)., Results: After itraconazole treatment, Filipin staining revealed cholesterol accumulation in the intracellular compartments, which was similar to the distribution after treatment of U18666A (cholesterol transport inhibitor). LC/MS analysis showed a significant decrease in phosphatidylserine levels and an increase in lysophosphatidylcholine levels in CaSki cells., Conclusion: Itraconazole inhibited cholesterol trafficking and altered the phospholipid composition. Alterations in the cell membrane can potentiate the anticancer activity of itraconazole., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Esophageal adenocarcinoma (EAC) derived from long-segment Barrett's esophagus (LSBE) is extremely rare in Asia. LSBE-related EAC is often difficult to diagnose in the horizontal extent. If the tumor has spread throughout the LSBE, whole circumferential endoscopic submucosal dissection (ESD) should be performed, which is difficult to complete safely. Additionally, whole circumferential ESD can bring refractory postoperative stenosis. We hereby report a case of EAC involving the whole circumference of the LSBE, achieving complete endoscopic removal without complications., Case Summary: An 85-year-old man with the chief complaint of dysphagia underwent esophagogastroduodenoscopy. We suspected a flat-type cancerous lesion that extended the whole circumference of the LSBE (C 3.5, M 4.0) using narrow-band imaging magnification endoscopy (NBI-M). We achieved circumferential en bloc resection of the lesion safely with special ESD techniques. Histology of the ESD specimens demonstrated that the superficial EAC extended the whole circumference of the LSBE, and papillary or well-differentiated tubular adenocarcinoma was confined in the lamina propria mucosa showing a vertical negative margin. To prevent post-ESD stenosis, we performed endoscopic local injection of steroids, followed by oral administration of steroids. There was no evidence of esophageal refractory stenosis or tumor recurrence 30 mo after ESD. In summary, we experienced a rare case of LSBE-related EAC. The horizontal tumor extent was accurately diagnosed by NBI-M. Additionally, we achieve whole circumferential ESD safely without postoperative refractory stenosis., Conclusion: NBI-M, ESD, and steroid therapy enabled the curative resection of superficial full circumferential LSBE-related EAC without refractory postoperative stenosis., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Kampo medicines contain many kinds of herbal drugs. Chinpi and Kippi, dried citrus peels, are components of a substantial number of Kampo medicine. They contain abundant flavonoids and studies on hesperidin, narirutin, and nobiletin as active ingredient have been conducted. Conversely, in Kagoshima prefecture, located in the southwestern part of the Japanese Islands, various citrus products are cultivated. Among them, Tankan and Daimasaki are specialies. In this study, we conducted high- performance liquid chromatography to determine the difference in flavonoid contents among Tankan, Daimasaki, Tankan related product, Chinpi, and Kippi. As a result, several active components, such as hesperidin, narirutin, nobiletin, and tangeretin, in common with crude drug, Chinpi, were detected in local citrus fruits. In addition, some active components little or not found in Chinpi, for example hesperetin and rutin, were detected in the local products. A detailed analysis of active components considering their genetic origin, the time of fruit collection, and different parts of the fruit used (peel, albedo, edible parts, and the whole) will need to be discussed to get the most out of the citrus fruits or make best use of them for health and longevity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the interaural direction, translational linear acceleration is loaded during lateral translational movement and gravitational acceleration is loaded during lateral tilting movement. These two types of acceleration induce eye movements via two kinds of otolith-ocular reflexes to compensate for movement and maintain clear vision: horizontal eye movement during translational movement, and torsional eye movement (torsion) during tilting movement. Although the two types of acceleration cannot be discriminated, the two otolith-ocular reflexes can distinguish them effectively. In the current study, we tested whether lateral-eyed mice exhibit both of these otolith-ocular reflexes. In addition, we propose a new index for assessing the otolith-ocular reflex in mice. During lateral translational movement, mice did not show appropriate horizontal eye movement, but exhibited unnecessary vertical torsion-like eye movement that compensated for the angle between the body axis and gravito-inertial acceleration (GIA; i.e., the sum of gravity and inertial force due to movement) by interpreting GIA as gravity. Using the new index (amplitude of vertical component of eye movement)/(angle between body axis and GIA), the mouse otolith-ocular reflex can be assessed without determining whether the otolith-ocular reflex is induced during translational movement or during tilting movement., (© 2021. The Author(s).)

Background: Superior mesenteric artery (SMA) syndrome is a well-known but relatively rare complication of anorexia nervosa. Although several reports have proposed surgery for SMA syndrome associated with anorexia nervosa, these have shown poor outcomes or did not reveal the long-term weight course. Thus, the long-term effectiveness of surgery for SMA syndrome in such cases remains unclear. This case report describes a patient with anorexia nervosa who underwent surgery for SMA syndrome., Case Presentation: An 18-year-old woman presented with anorexia nervosa when she was 16 years old. She also presented with SMA syndrome, which seemed to be caused by weight loss due to the eating disorder. Nutrition therapy initially improved her body weight, but she ceased treatment. She reported that symptoms related to SMA syndrome had led to her weight loss and desired to undergo surgery. Laparoscopic duodenojejunostomy was performed, but her body weight did not improve after the surgery. The patient eventually received conservative nutritional treatment along with psychological approaches, which led to an improvement in her body weight., Conclusions: The case implies that surgery for SMA syndrome in patients with anorexia nervosa is ineffective for long-term weight recovery and that conservative treatment can sufficiently improve body weight; this is consistent with the lack of evidence on the topic and reports on potential complications of surgery. Due to difficulties in assessing psychological status, consultation with specialists on eating disorders is necessary for treating patients with severely low body weight.

This study compares the performance of nanosecond pulse (NSP) and direct current (DC) power supplies for use in a municipal wastewater treatment by electrocoagulation (EC). Four Al plates connected in monopolar-parallel configuration (MP-P) were used as electrodes during the EC process. The maximum chemical oxygen demand (COD) removal efficiency reached 68% and 80% using DC and NSP, respectively. Moreover, NSP treatment reduced approximately 15% of the specific energy consumption (SEC) compared with that by DC at a similar COD removal efficiency of ≈ 68%, which was used as a benchmark value. In addition, when using NSP, the SEC required to increase the COD removal efficiency from 60% to 68% was two to three times less than that when DC was applied. The results suggest that an NSP operating at 10 kHz frequency ( f ) and 1 µs pulse width ( pw ) are preferred for obtaining higher COD removal efficiencies at a low SEC. The use of an NSP for EC can enhance the COD removal efficiency and reduce the wastewater treatment SEC. The results presented herein promote the use of EC systems combined with renewable energy sources for reducing the net carbon footprint of wastewater processing.

The aim of this study was to evaluate the contribution of dissolved organic carbon (DOC) and microbial community dynamics to membrane fouling development in membrane bioreactor (MBR). We operated laboratory-scale anoxic/oxic-MBRs under prolonged starvation conditions in different seasons and the dynamics and diversity of the microbial communities were investigated. Although fouled-MBRs showed DOC accumulation in the activated sludge (AS), the fouling-mitigated MBR suggested that dissolved oxygen was consumed and DOC of the sludge supernatant was degraded. 16S rRNA genes analysis of AS in the MBRs revealed that Chitinophagaceae and Candidatus Promineofilum specifically increased in the fouling-mitigated MBR, suggesting that they played important roles in membrane fouling mitigation; high microbial diversity in the reactor also contributed to fouling mitigation. In the fouled reactor, enrichment of Xanthomonadaceae might be related to fouling causing substances formation leading to membrane fouling development; lower microbial diversity also contributed to fouling development in the fouled MBR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pancreatic cancer is the most lethal solid malignancy, and the number of patients with pancreatic cancer is increasing. Systemic chemotherapies are often ineffective for such patients, and there is an urgent need for personalized medicine. Unlike other types of cancer, personalized treatments for pancreatic cancer are still in development. Consequently, pancreatic cancer is less sensitive to anticancer drugs and is often refractory to common treatments. Therefore, advances in personalized medicine for pancreatic cancer are necessary. This review examined advances in personalized medicine for pancreatic cancer, including the use of endoscopic ultrasound (EUS)-guided sampling. EUS-guided sampling is widely used for diagnosing pancreatic tumors and is expected to be applied to sampled tissues. Additionally, there has been an increase in clinical research using EUS-guided sampling. The combination of precision medicine using genomic testing and pharmacological profiles based on high-throughput drug sensitivity testing using patient-derived organoids is expected to revolutionize pancreatic cancer treatment.

In 2009, diagnostic criteria for early chronic pancreatitis (DCECP2009) were proposed by the Japan Pancreas Society. This study aimed to evaluate the interobserver reliability (IOR) of endoscopic ultrasound (EUS) criteria for diagnosis of early chronic pancreatitis (ECP) between DCECP2009 and 2019 diagnostic criteria for ECP (DCECP2019) to assess the validity of the revision from the perspective of EUS findings. Among patients who underwent a detailed observation of the pancreas by EUS at our institution between January 2018 and March 2019, EUS images of 97 patients were extracted. Images were reviewed by 12 gastrointestinal endoscopy experts (eight pancreatologists, group A and four nonpancreatologists, group B). The overall kappa (K)-values for the IOR of the DCECP2009 EUS criteria were 0.424 and 0.563:0.231 for groups A:B, whereas the overall K-values for the DCECP2019 criteria were 0.618, and 0.733:0.442 for groups A:B. Regarding changes in the final diagnosis of ECP based on clinical features and EUS findings, 20 cases were definite ECP, 53 were probable ECP, and 24 were normal according to DCECP2009. In contrast, seven were definite ECP, 19 were probable ECP, and 71 were normal according to DECEP2019. IOR of DCECP2019 was higher than that of DCECP2009, which indicates an improvement in precision.

Biofilm development on the membrane surface is one of the main reasons for membrane fouling in membrane bioreactors (MBRs) and it is a big problem for their stable operation. Precise information on the microbial community composition of the biofilm is needed for a better understanding of biofilm development. However, there have been limited investigations of the relationship between the biofilm formation process and the microbial community of activated sludge and biofilm in MBRs treating real sewage. In this study, relationships between the microbial community structure of biofilm and activated sludge at each biofilm formation stage were investigated and biofilm growth was elucidated by nondestructive observations. Two anoxic/oxic MBRs were operated and membrane fouling was induced. Permeability rapidly decreased in both reactors and live cell microcolonies were formed on dead cell conditioning film on the membrane surface. Principal component analysis based on 16S rRNA gene sequences showed that the biofilm microbial community changed significantly from middle stage to mature biofilm when compared with that of activated sludge. The abundance of specific bacteria, such as unclassified Neisseriaceae, increased in middle-stage biofilm and the diversity indexes of middle-stage biofilm were lower than those of mature biofilm and activated sludge. These results suggested that the presence of specific bacteria with colonization ability played a crucial role in biofilm formation. Strategies are needed to target membrane fouling mitigation during early- and middle-stage biofilm formation to reduce MBR membrane fouling. KEY POINTS: • Microbial community of mature biofilm was approached to that of activated sludge. • In the middle-stage biofilm, live cells colonized on a dead-cell-conditioning-film. • Microbial diversity was lower in live cell colonizing stage than in activated sludge.

Background: Endoscopic transpapillary stenting is commonly performed in patients with obstructive jaundice caused by a biliary stricture. Although the plastic stent (PS) is widely used for biliary drainage because of the low-cost and easy procedure, patency is short after placement in the bile duct because of the small diameter. Dysfunction of PS is primarily caused by biliary sludge that forms as a result of bacterial adhesion and subsequent biofilm formation on the inner surface of the stent. It is well known that silver ions have excellent antibacterial activity against a wide range of microorganisms., Objective: This review provides an overview and perspective of the significance of silver-coated biliary stents., Methods: We collected literature regarding silver-coated biliary stents, reviewed the current research/development status and discussed their possible usefulness., Results: To date, several in vivo/vitro studies evaluated the patency of silver-blended or silver-coated biliary stents. These studies suggested that the silver coating on a PS was likely to prolong the patency period., Conclusion: The development of biliary stents using silver is expected to prolong stent patency and prevent frequent stent replacement.

Three-dimensional high-resolution late gadolinium enhancement (3D HR LGE) magnetic resonance imaging (MRI) using compressed sensing can help detect small myocardial infarcts. We discuss the case of an 11-year-old child with an anomalous aortic origin of the left coronary artery. Since he was suspected to have coronary stenosis due to anomalous aortic origin of the left coronary artery, cardiovascular MRI, including conventional two-dimensional (2D) LGE MRI and HR 3D LGE MRI, was conducted. Myocardial scars were not clearly observed via 2D LGE MRI; however, 3D HR MRI revealed subendocardial infarction of the anteroseptal wall, which corresponded to the left coronary artery. By applying the compressed sensing technique, 3D HR LGE, MRI enables a detailed assessment of small myocardial infarcts in a clinically feasible scan time., (© 2020 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

The concept of mental capacity refers to the a bility to understand medical explanations and make decisions with reference to values. Evaluating mental capacity is associated with patient autonomy and mental capacity is clinically and ethically important. In competent patients, patient self-determination is respected. On the other hand, in incompetent patients, "best interest" is presumed in terms of medical fact and patient value.

Background: The present study aimed to characterize factors associated with patients issued DNR orders during hospitalization who are discharged alive without any instruction orders by physicians regarding end-of-life treatment, with a focus on the timing of DNR order issuance., Methods: In total, 2997 DNR cases from all 61,037 patients aged ≥20 years admitted to a representative general hospital in Tokyo were extracted and divided into two groups by patient hospital release status (discharged alive/deceased). Study items included age, sex, disease type (non-cancer/cancer), hospital department (internal medicine/others), timing of DNR order issuance, implementation (or not) of life-sustaining treatment (LST) or the presence of any restrictions on LST and hospital length of stay. We conducted multiple logistic regression analysis, setting hospital release status as the dependent variable and each above study item as explanatory variables., Results: DNR orders were issued at a rate of 4.9%. The analysis revealed that patients with a DNR who were ultimately discharged alive were statistically more likely to be those for whom DNR orders are issued early after admission (adjusted odds ratio: AOR, 13.7), non-cancer patients (AOR, 3.4), internal medicine department patients (AOR, 1.63), females (AOR, 1.34), and elderly (aged ≥85 years; AOR, 1.02); these patients were also less likely to be receiving LST (AOR, 0.36)., Conclusions: By focusing on those with DNR orders who were ultimately discharged alive, we discovered that these patients were likely to have DNR orders issued early after admission, and that they were more likely to be elderly, female, non-cancer patients, or those in internal medicine departments. Further examination of these data may help to elucidate why these particular DNR-related characteristics (including socio-economic and cultural factors) are evident in patients who end up being discharged alive.

Objectives: Early enteral nutrition is recommended for patients with severe acute pancreatitis (AP); however, nutritional management strategies for patients with mild AP have not been established. The aim of this study was to evaluate the benefits and safety of immediate oral intake of low-fat solid food in patients with mild AP who were allowed to take opioid analgesics., Methods: In this single-center randomized study, the immediate feeding (IMF) group was permitted immediate oral intake of low-fat (15 g/d) solid food. In the standard food (STF) group, patients received gradually increasing amounts of dietary fat. Twenty-six patients were randomized, with 13 allocated to each group. The primary outcome was the period between diagnosis and recovery from AP. The cost and rate of progression to severe disease were evaluated as secondary outcomes., Results: The IMF group (mean recovery days: 2 ± 1) recovered significantly earlier (mean difference in recovery days: 6.3; 95% confidence interval [CI], 4.8-7.9; P < 0.001) than the STF group (mean recovery days: 8.3 ± 2.3), with a lower overall treatment cost (mean difference in costs: -$460; 95% CI, -$880 to -$40; P = 0.034). The IMF group showed a lower rate of progression to severe AP (IMF, 0%; STF, 15.3%; P = 0.48)., Conclusion: The initial treatment strategy for mild AP should be altered from the gradual introduction of oral feeding upon the absence of pain to immediate oral nutrition with opioid analgesics, to improve treatment efficacy and reduce treatment cost., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

Amyloidosis of the uterine cervix is rare. A 35-year-old pregnant woman underwent a cervical biopsy and was found to have amyloid deposits. The results of liquid chromatography-tandem mass spectrometry revealed that these deposits mainly consisted of immunoglobulin light chain (kappa chain). After undergoing several examinations, the patient was diagnosed with localized amyloidosis, without systemic or secondary amyloidosis. She underwent a normal delivery without disease exacerbation. The possible presence of systemic and secondary amyloidosis must be evaluated carefully during the diagnosis of localized cervical amyloidosis., (© 2020 Japan Society of Obstetrics and Gynecology.)

Sulfur (S) assimilation, which is initiated by sulfate uptake, generates cysteine, the substrate for glutathione (GSH) and phytochelatin (PC) synthesis. GSH and PC contribute to cadmium (Cd) detoxification by capturing it for sequestration. Although Cd exposure is known to induce the expression of S-assimilating enzyme genes, including sulfate transporters (SULTRs), mechanisms of their transcriptional regulation are not well understood. Transcription factor SLIM1 controls transcriptional changes during S deficiency (-S) in Arabidopsis thaliana. We examined the potential involvement of SLIM1 in inducing the S assimilation pathway and PC accumulation. Cd treatment reduced the shoot fresh weight in the sulfur limitation1 (slim1) mutant but not in the parental line (1;2PGN). Cd-induced increases of sulfate uptake and SULTR1;2 expressions were diminished in the slim1 mutant, suggesting that SLIM1 is involved in inducing sulfate uptake during Cd exposure. The GSH and PC levels were lower in slim1 than in the parental line, indicating that SLIM1 was required for increasing PC during Cd treatment. Hence, SLIM1 indirectly contributes to Cd tolerance of plants by inducing -S responses in the cell caused by depleting the GSH pool, which is consumed by enhanced PC synthesis and sequestration to the vacuole., Competing Interests: The authors have no conflicts of interest to declare.

Objective: Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection., Methods: This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints., Results: Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04)., Conclusions: The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts., Registry and the Registration Number: The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382)., (© 2019 Japan Gastroenterological Endoscopy Society.)

Background and study aims  Endoscopic papillectomy (EP) is a minimally invasive treatment for ampullary neoplasms and is recognized as an alternative treatment to surgical resection; however, there are few reports on a suitable pancreatic stent (PS) after EP for preventing pancreatitis. The aim of this study was to evaluate the efficacy of a long PS after EP. Patients and methods  In this retrospective single-center study, 39 patients with pathologically proven ampullary neoplasms who underwent EP between March 2012 and August 2018 were enrolled. The study participants were divided into two subgroups according to the PS length: those with a PS shorter than 5 cm (short PS group, n = 17) and those with a PS of 7 cm (long PS group, n = 22). The incidence of adverse events and risk factors for pancreatitis were evaluated. Results  The diameter of all PSs was 5 Fr. Post-EP pancreatitis occurred in nine patients (23.1 %), with two cases of severe pancreatitis (5.1 %). Pancreatitis occurred more frequently in the short PS group (7/17, 41.2 %) than in the long PS group (2/22, 9.1 %) ( P  = 0.026). There were no significant differences between the two groups in terms of other adverse events. Univariate and multivariate analyses showed that a long PS was the only factor associated with a decreased incidence of post-EP pancreatitis ( P  = 0.042; odds ratio, 0.16; 95 % confidence interval, 0.027-0.94). Conclusion  A long (7 cm) PS significantly decreased incidence of pancreatitis after EP. Prospective randomized studies with a larger number of patients and wider range of PS lengths are required., Competing Interests: Competing interests None

When vestibular function is lost, vestibular compensation works for the reacquisition of body balance. For the study of vestibular dysfunction and vestibular compensation, surgical or chemical labyrinthectomy has been performed in various animal species. In the present study, we performed chemical labyrinthectomy using arsanilic acid in mice and investigated the time course of vestibular compensation through behavioral observations and histological studies. The surgical procedures required only paracentesis and storage of 50 µL of p -arsanilic acid sodium salt solution in the tympanic cavity for 5 min. From behavioral observations, vestibular functions were worst at 2 days and recovered by 7 days after surgery. Spontaneous nystagmus appeared at 1 day after surgery with arsanilic acid and disappeared by 2 days. Histological studies revealed specific damage to the vestibular endorgans. In the ipsilateral spinal vestibular nucleus, the medial vestibular nucleus, and the contralateral prepositus hypoglossal nucleus, a substantial number of c-Fos-immunoreactive cells appeared by 1 day after surgery with arsanilic acid, with a maximum increase in number by 2 days and complete disappearance by 7 days. Taken together, these findings indicate that chemical labyrinthectomy with arsanilic acid and the subsequent observation of vestibular compensation is a useful strategy for elucidation of the molecular mechanisms underlying vestibular pathophysiologies.

Objective Risks of bleeding and pancreatitis after mucosal resection using the purecut/autocut and blendcut/endocut modes for endoscopic papillectomy have not been fully clarified. Thus, a systematic review on electrosurgical cutting modes for endoscopic papillectomy was conducted focusing on the types and incidence of adverse events. Methods We searched the PubMed and Cochrane library for cases of endoscopic papillectomy recorded as of April 2017. Studies reporting the methods of electrically excising a tumor in the duodenal papilla and the number of adverse events were extracted. Studies were collected and examined separately based on the electrosurgical cutting mode, and the incidence rate for each adverse event was summarized. Results A total of 159 relevant articles were found; among them, 20 studies were included and 139 excluded. Five studies analyzed endoscopic papillectomy with the purecut/autocut mode and 16 with the blendcut/endocut mode. Only one study investigated both modes (purecut and endocut). With the purecut/autocut mode, the incidence of bleeding was 2.8-50%, and that of pancreatitis was 0-50% (mean: 12.8%). With the blendcut/endocut mode, the incidence of bleeding was 0-42.3%, and that of pancreatitis was 0%-17.9% (mean: 9.5%). Conclusion Both methods had high adverse event rates for endoscopic papillectomy. Thus, a standard method of endoscopic papillectomy, including the electrosurgical cutting mode, needs to be established.

Introduction: Although guidelines do not recommend chemotherapy for patients with advanced cancer when death is imminent, many reports suggest the tendency to continue this treatment has been increasing every year. This study aimed to construct a model to clarify the beliefs and communication of doctors who administer chemotherapy to patients with recurrent or metastatic (hereafter, "recurrent/metastatic") breast cancer, and determine how these beliefs are related to the process of treating patients., Materials and Methods: Semi-structured interviews were conducted with 21 breast surgeons, and interview contents were analyzed using the grounded theory approach in order to conceptualize the treatment process., Results: The process of chemotherapy for patients with recurrent/metastatic breast cancer differed based on two beliefs held by doctors. One was a "belief that the patient is an entity who cannot accept death," and throughout the treatment process, these doctors consistently avoided sharing bad news that might hurt patients, and always discussed aggressive chemotherapy. They proposed treatments as long as options remained, and when they ultimately judged that the physical condition of patients could not withstand further treatment, treatment was terminated despite the patient hoping for continuation. The other was a "belief that the patient is an entity who can accept death." From early on after recurrence/metastasis, these doctors repeatedly gave patients information including bad news about prognosis, and when they judged that further treatment would hinder a patient's ability to have a good death, they proposed terminating treatment., Conclusion: We demonstrated that breast surgeons treating recurrent/metastatic breast cancer patients have two beliefs and constructed a model of the treatment process based on those beliefs. This offered breast surgeons, who make decisions regarding treatment without clearly-defined guidelines, a chance to reflect on their own care style, which we believe will contribute to optimal patient care., Competing Interests: Dr Taichi Hatta reports grants from Supporting Program for InteRaction-based Initiative Team Studies (SPIRITS), Research Institute of Science and Technology for Society (RISTEX), outside the submitted work. The authors report no other conflicts of interest in this work.

The sphenopalatine ganglion (SPG) is a gathering of the cell bodies of parasympathetic fibers that dominate the nasal gland, lacrimal gland and cerebral blood vessels. The SPG controls nasal secretions, tears, and the dilation of cerebral blood vessels. However, it is unclear how serotonin regulates SPG functions. In this study, we investigated the expression of genes involved in the serotonergic system in the mouse SPG. We examined the mRNA expression levels of 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 1F , 5-HT 2A , 5-HT 2B , 5-HT 2C , 5-HT 3A , 5-HT 3B , 5-HT 4 , 5-HT 5A , 5-HT 5B , 5-HT 6 and 5-HT 7 receptors, as well as serotonin transporter, tryptophan hydroxylases 1 and 2, and L-amino acid decarboxylase (AADC) by RT-PCR. It revealed that the 5-HT 3A and 5-HT 3B ionotropic receptors and AADC were likely to be highly expressed in the SPG, as measured by RT-PCR. We next performed in situ hybridization on the SPG to examine the expression of these three genes at the cellular level after validating the specificity of each cRNA probe by northern blotting. The 5-HT 3A receptor, 5-HT 3B receptor, and AADC were expressed in 96.5% ± 1.0%, 29.7% ± 10.7%, and 57.4% ± 2.9% of neuronal cell bodies in the SPG, respectively, indicating that the 5-HT 3A receptor was virtually expressed in all SPG neurons. Our results on the expression of these critical serotonin system genes in the parasympathetic SPG provide insight into the pathogenetics of rhinitis, conjunctivitis and headache. Furthermore, our findings suggest that targeting the 5-HT 3A receptor might have therapeutic potential in the treatment of these ailments., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) and related disorders are characterized by filamentous or fibrous structures consisting of abnormal α-synuclein in the brains of patients, and the distributions and spread of these pathologies are closely correlated with disease progression. L-DOPA (a dopamine precursor) is the most effective therapy for PD, but it remains unclear whether the drug has any effect on the formation and propagation of pathogenic abnormal α-synuclein in vivo . Here, we tested whether or not L-DOPA influences the prion-like spread of α-synuclein pathologies in a wild-type (WT) mouse model of α-synuclein propagation. To quantitative the pathological α-synuclein in mice, we prepared brain sections stained with an anti-phosphoSer129 (PS129) antibody after pretreatments with autoclaving and formic acid, and carefully analyzed positive aggregates on multiple sections covering the areas of interest using a microscope. Notably, a significant reduction in the accumulation of phosphorylated α-synuclein was detected in substantia nigra of L-DOPA/benserazide (a dopamine decarboxylase inhibitor)-treated mice, compared with control mice. These results suggest that L-DOPA may slow the progression of PD in vivo by suppressing the aggregation of α-synuclein in dopaminergic neurons and the cell-to-cell propagation of abnormal α-synuclein. This is the first report describing the suppressing effect of L-DOPA/benserazide on the propagation of pathological α-synuclein. The experimental protocols and detection methods in this study are expected to be useful for evaluation of drug candidates or new therapies targeting the propagation of α-synuclein.

Objective: This study was performed to determine whether endolymphatic sac surgery improves vestibular and cochlear endolymphatic hydrops 2 years after sac surgery and to elucidate the relationship between the degree of improvement of endolymphatic hydrops and the changes in vertigo symptoms, the hearing level, and the summating potential/action potential ratio (-SP/AP ratio) by electrocochleography (ECochG) in patients with Ménière's disease (MD)., Methods: Twenty-one patients with unilateral MD who underwent sac surgery were included in this study. All patients underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI) before and 2 years after sac surgery. We evaluated the difference in vestibular and cochlear endolymphatic hydrops between before and after surgery in both ears and compared these findings with the frequency of vertigo attacks, hearing level, and ECochG findings., Results: In affected ears, the presence of vestibular endolymphatic hydrops and the frequency of vertigo attacks significantly decreased after surgery. However, affected ears showed no significant improvement in the presence of cochlear endolymphatic hydrops or the -SP/AP ratio by ECochG; there was also no significant improvement or deterioration in the hearing level., Conclusion: The present findings suggest that sac surgery reduces vestibular endolymphatic hydrops and prevents aggravation of cochlear endolymphatic hydrops, and these changes lead to a reduction of vertigo attacks and suppress the progression of hearing impairment associated with vertigo attacks., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: There is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO 2 insufflation., Methods: Non-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO 2 (EtCO 2 ) was continuously monitored during the procedure under CO 2 insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO 2 ) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system., Results: Eleven patients were enrolled. Measurement of EtCO 2 concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s)., Conclusion: This study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO 2 concentration using the newly developed mainstream capnometer system was feasible and safe even under CO 2 insufflation., Competing Interests: Competing interests: TM received research grant from Nihon Kohden, Tokyo, Japan.

The major symptoms of Ménière's disease are episodic vertigo, fluctuating hearing loss, and tinnitus. Direction-changing spontaneous nystagmus is a characteristic vestibular finding in Ménière's disease. In the acute stage, spontaneous nystagmus beating to the affected side (irritative nystagmus) is often observed, while paralytic nystagmus beating to the healthy side is found in the chronic stage. This direction-changing nystagmus can be reproduced in guinea pigs by increasing the potassium ion concentration in the perilymph. The objectives of the present study were to examine the effects of increasing the potassium ion concentration of the rat perilymph on hearing and nystagmus. Under isoflurane anesthesia, 22 rats received intratympanic injection of different concentrations of potassium chloride (KCl) solution or distilled water: groups 1, 2, 3, and 4 received saturated (3.4 M) KCl solution, 2 M KCl, 1 M KCl, and distilled water, respectively. The nystagmus direction and number per 15 s were monitored for 150 min. In the other 8 rats, hearing was monitored 30 min and 20 h after intratympanic injection of 2 M KCl (group 5) or distilled water (group 6) using the auditory brainstem responses. Rats in groups 1 and 2 showed spontaneous irritative nystagmus beating to the affected ear followed by paralytic nystagmus beating to the contralateral side. In group 3, irritative nystagmus occurred but paralytic nystagmus was rarely observed. Rats in group 4 showed no nystagmus. Rats in group 5 showed significant hearing impairment 30 min after KCl injection that recovered 20 h later. Control animals in group 6 showed no significant changes in hearing. The reversible hearing impairment with direction-changing spontaneous nystagmus induced by potassium injection into the tympanic cavity in rats was quite similar to that observed in acute Ménière's attacks. This rat model could be used for basic research investigating the pathophysiological mechanisms underlying Ménière's attacks., (© 2019 S. Karger AG, Basel.)