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Physician-patient disputes are a major problem in healthcare. Physician-patient conflicts, workplace violence, and direct involvement in disputes have a significant negative impact on the well-being of physicians. China and Japan have similar cultures but differing healthcare systems. The present study aimed to examine and compare the experiences and perceptions of Chinese and Japanese physicians regarding medical disputes. Qualitative descriptive content analysis was performed for 18 cases from each country to assess the major issues involved in each case and their impact on the physicians. Common issues in medical disputes for both countries included monetary motives of patients and/or families, violence/threats from patients and/or families, the inability of patients and/or families to understand the risk of complications, and the uncertainties of medicine. The serious impact of medical disputes on the mental health and professionalism of physicians was also an issue shared by physicians of both countries. There were, however, differences in the magnitude and frequency of these issues between the two countries. Pre-existing distrust of physicians among patients and/or families was noted only by Chinese physicians, and insufficient information disclosure by physicians was noted only by Japanese physicians. In conclusion, there were similarities and differences between the two countries in the perceptions of physicians regarding medical disputes. Our analysis revealed differing healthcare situations due to cultural and institutional differences as well as universal problems intrinsic to medicine. Based on our results, we propose several key principles to improve the physician-patient relationship., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2024.)

Background: Healthcare professionals use the ethics of justice and care to construct moral reasoning. These ethics are conflicting in nature; different value systems and orders of justice and care are applied to the cause of actual moral conflict. We aim to clarify the structure and factors of healthcare professionals' moral conflicts through the lens of justice and care to obtain suggestions for conflict resolutions., Method: Semi-structured interviews about experiences of moral conflict were conducted with Japanese nurses recruited using the snowball sampling method. Interviews were conducted based on the real-life moral conflict and choice interview. Interviews were recorded and transcribed verbatim, then analyzed based on the interpretive method of data analysis. Verbatim transcripts were read four times, first to get an overall sense of the conflict, then to understand the person's thoughts and actions that explain the conflict, and third and fourth to identify perspectives of justice and care, respectively. Each moral perspective was classified into categories according to Chally's taxonomy., Results: Among 31 responses, 2 that did not mention moral conflict were excluded, leaving 29 responses that were analyzed. These responses were classified into six cases with conflict between both justice and care perspectives or within one perspective, and into two cases without conflict between perspectives. The "rules" category of justice and the "welfare of others" category of care were included in many cases of conflict between two perspectives, and they frequently occurred in each perspective., Conclusions: The nurses in this study suggest that they make moral judgments based on moral values that are intertwined with justice and care perspectives complex manner.Organizational, professional, and patient-related factors influenced conflicts between justice and care. Additionally, multiple overlapping loyalties created conflicts within justice perspectives, and multifaceted aspects of care-provider's responsibility and patient need created conflicts within care. Decision-making biased towards one perspective can be distorted. It is important to consider ethical issues from both perspectives to resolve conflicts, especially the effective use of the ethics of care is recommended., (© 2023. BioMed Central Ltd., part of Springer Nature.)

CCCTC-binding factor (CTCF) has a key role in higher-order chromatin architecture that is important for establishing and maintaining cell identity by controlling gene expression. In the mature cerebellum, CTCF is highly expressed in Purkinje cells (PCs) as compared with other cerebellar neurons. The cerebellum plays an important role in motor function by regulating PCs, which are the sole output neurons, and defects in PCs cause motor dysfunction. However, the role of CTCF in PCs has not yet been explored. Here we found that the absence of CTCF in mouse PCs led to progressive motor dysfunction and abnormal dendritic morphology in those cells, which included dendritic self-avoidance defects and a proximal shift in the climbing fibre innervation territory on PC dendrites. Furthermore, we found the peculiar lamellar structures known as "giant lamellar bodies" (GLBs), which have been reported in PCs of patients with Werdnig-Hoffman disease, 13q deletion syndrome, and Krabbe disease. GLBs are localized to PC dendrites and are assumed to be associated with neurodegeneration. They have been noted, however, only in case reports following autopsy, and reports of their existence have been very limited. Here we show that GLBs were reproducibly formed in PC dendrites of a mouse model in which CTCF was deleted. GLBs were not noted in PC dendrites at infancy but instead developed over time. In conjunction with GLB development in PC dendrites, the endoplasmic reticulum was almost absent around the nuclei, the mitochondria were markedly swollen and their cristae had decreased drastically, and almost all PCs eventually disappeared as severe motor deficits manifested. Our results revealed the important role of CTCF during normal development and in maintaining PCs and provide new insights into the molecular mechanism of GLB formation during neurodegenerative disease., (© 2022. The Author(s).)

Cadaver surgical training (CST), which aims to maintain patient safety, provided anatomists with new duties and increased their workload. In Japan, with development of relevant guidelines, CST programs have been implemented and promoted mainly by surgical societies. This paper examines ethics of and anatomists' attitude toward the Japanese CST guidelines. The guidelines were well established to ensure that ethical issues such as financial exploitation and commercialism involved in procurement of cadavers for training do not emerge, as these can create the dilemma of how to allocate cadavers for undergraduate education and postgraduate surgical training, given the increase in demand for cadavers. Fair allocation must accommodate and respect the donor's advance will. Also, the guidelines must offer more detailed commentary on informed consent, particularly with regard to disclosure of information to donor candidates. The guidelines should explain better the legality of CST, the roles of anatomists, and surgeon preparedness., (© 2022. The Author(s), under exclusive licence to Japanese Association of Anatomists.)

Background: We have developed the bispectral electroencephalography (BSEEG) method for detection of delirium and prediction of poor outcomes., Aims: To improve the BSEEG method by introducing a new EEG device., Method: In a prospective cohort study, EEG data were obtained and BSEEG scores were calculated. BSEEG scores were filtered on the basis of standard deviation (s.d.) values to exclude signals with high noise. Both non-filtered and s.d.-filtered BSEEG scores were analysed. BSEEG scores were compared with the results of three delirium screening scales: the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), the Delirium Rating Scale-Revised-98 (DRS) and the Delirium Observation Screening Scale (DOSS). Additionally, the 365-day mortalities and the length of stay (LOS) in the hospital were analysed., Results: We enrolled 279 elderly participants and obtained 620 BSEEG recordings; 142 participants were categorised as BSEEG-positive, reflecting slower EEG activity. BSEEG scores were higher in the CAM-ICU-positive group than in the CAM-ICU-negative group. There were significant correlations between BSEEG scores and scores on the DRS and the DOSS. The mortality rate of the BSEEG-positive group was significantly higher than that of the BSEEG-negative group. The LOS of the BSEEG-positive group was longer compared with that of the BSEEG-negative group. BSEEG scores after s.d. filtering showed stronger correlations with delirium screening scores and more significant prediction of mortality., Conclusions: We confirmed the usefulness of the BSEEG method for detection of delirium and of delirium severity, and prediction of patient outcomes with a new EEG device.

Purpose: Cancer patients in university hospitals often face a difficult decision regarding transfer to other care settings at the end-of-life. Arrangements for a satisfying transfer are important for reducing the psychosocial impact of the transition, but few studies have evaluated this aspect. This study aimed to identify factors related to the satisfying arrangement of transfers to other care settings from university hospitals., Methods: A total of 400 bereaved family members of cancer patients in Japan participated in this cross-sectional web-based questionnaire survey. Statistical methods including decision tree analysis were conducted to identify factors significantly associated with satisfying transfer arrangements., Results: More than 60% of cancer patients were satisfied with the transfer arrangements made by university hospitals. Decision tree analysis revealed that the factor most significantly associated with satisfaction with transfer arrangements was "satisfaction with contents of the explanation about transfer." The following significant factors were also extracted: "timing of being informed of transfer," "presence of primary care physician," and "presence of trustworthy staff." "Satisfaction with overall care from university hospital staff" and "involvement of palliative care team" were identified as factors contributing to a high degree of satisfaction with transfer arrangements., Conclusion: In order to make satisfying transfer arrangements from university hospitals for cancer patients at the end-of-life, healthcare professionals should provide satisfactory explanations about the transfer process in order to meet the information needs of patients. To be effective, healthcare professionals should initiate transfer arrangements prior to cancer treatment, while simultaneously building trusting relationships with patients.

Current methods for screening and detecting delirium are not practical in clinical settings. We previously showed that a simplified EEG with bispectral electroencephalography (BSEEG) algorithm can detect delirium in elderly inpatients. In this study, we performed a post-hoc BSEEG data analysis using larger sample size and performed topological data analysis to improve the BSEEG method. Data from 274 subjects included in the previous study were analyzed as a 1st cohort. Subjects were enrolled at the University of Iowa Hospitals and Clinics (UIHC) between January 30, 2016, and October 30, 2017. A second cohort with 265 subjects was recruited between January 16, 2019, and August 19, 2019. The BSEEG score was calculated as a power ratio between low frequency to high frequency using our newly developed algorithm. Additionally, Topological data analysis (TDA) score was calculated by applying TDA to our EEG data. The BSEEG score and TDA score were compared between those patients with delirium and without delirium. Among the 274 subjects from the first cohort, 102 were categorized as delirious. Among the 206 subjects from the second cohort, 42 were categorized as delirious. The areas under the curve (AUCs) based on BSEEG score were 0.72 (1st cohort, Fp1-A1), 0.76 (1st cohort, Fp2-A2), and 0.67 (2nd cohort). AUCs from TDA were much higher at 0.82 (1st cohort, Fp1-A1), 0.84 (1st cohort, Fp2-A2), and 0.78 (2nd cohort). When sensitivity was set to be 0.80, the TDA drastically improved specificity to 0.66 (1st cohort, Fp1-A1), 0.72 (1st cohort, Fp2-A2), and 0.62 (2nd cohort), compared to 0.48 (1st cohort, Fp1-A1), 0.54 (1st cohort, Fp2-A2), and 0.46 (2nd cohort) with BSEEG. BSEEG has the potential to detect delirium, and TDA is helpful to improve the performance.

For treatment of complex congenital heart disease, computer simulation using a three-dimensional heart model may help to improve outcomes by enabling detailed preoperative evaluations. However, no highly integrated model that accurately reproduces a patient's pathophysiology, which is required for this simulation has been reported. We modelled a case of complex congenital heart disease, double outlet right ventricle with ventricular septal defect and atrial septal defect. From preoperative computed tomography images, finite element meshes of the heart and torso were created, and cell model of cardiac electrophysiology and sarcomere dynamics was implemented. The parameter values of the heart model were adjusted to reproduce the patient's electrocardiogram and haemodynamics recorded preoperatively. Two options of in silico surgery were performed using this heart model, and the resulting changes in performance were examined. Preoperative and postoperative simulations showed good agreement with clinical records including haemodynamics and measured oxyhaemoglobin saturations. The use of a detailed sarcomere model also enabled comparison of energetic efficiency between the two surgical options. A novel in silico model of congenital heart disease that integrates molecular models of cardiac function successfully reproduces the observed pathophysiology. The simulation of postoperative state by in silico surgeries can help guide clinical decision-making.

The Human Papillomavirus (HPV) vaccine was integrated into Japan's national immunization program (NIP) in April 2013. However, numerous instances of serious adverse reactions were widely reported in the media, resulting in the Ministry of Health, Labor, and Welfare (MHLW) suspending the official recommendation of the HPV vaccine on June 14, 2013. Investigating the reported incidents, the Vaccine Adverse Reactions Review Committee (VARRC)-an MHLW advisory committee-found no high-quality evidence supporting a causal relationship between the reported events and the HPV vaccination. However, rather than lifting the suspension, they have opted to maintain a "pseudo informed consent" confirming the perceptions of Japanese citizens regarding the vaccine. Accordingly, there appears to be a fundamental difference in the approach to vaccine policymaking between Japan (MHLW/VARRC) and other countries and the World Health Organization, which base policy decisions on the effectiveness and safety of the vaccine. Consequently, the arguments for the suspension of the HPV vaccine recommendation are not ethically appropriate. Relevant bodies must make a clear decision regarding the HPV vaccine and its status in the NIP: the proactive recommendation must either be reinstated or the HPV vaccine legal framework altered to rely entirely on voluntary individual decisions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Destination therapy (DT) is the permanent implantation of a left ventricular assist device (LVAD) in patients with end-stage, severe heart failure who are ineligible for heart transplantation. DT improves both the quality of life and prognosis of patients with end-stage heart failure. However, there are also downsides to DT such as life-threatening complications and the potential for the patient to live beyond their desired length of life following such major complications. Because of deeply ingrained cultural and religious beliefs regarding death and the sanctity of life, Japanese society may not be ready to make changes needed to enable patients to have LVADs deactivated under certain circumstances to avoid needless suffering., Main Text: Western ethical views that permit LVAD deactivation based mainly on respect for autonomy and dignity have not been accepted thus far in Japan and are unlikely to be accepted, given the current Japanese culture and traditional values. Some healthcare professionals might regard patients as ineligible for DT unless they have prepared advance directives. If this were to happen, the right to prepare an advance directive would instead become an obligation to do so. Furthermore, patient selection for DT poses another ethical issue. Given the predominant sanctity of life principle and lack of cost-consciousness regarding medical expenses, medically appropriate exclusion criteria would be ignored and DT could be applied to various patients, including very old patients, the demented, or even patients in persistent vegetative states, through on-site judgment., Conclusion: There is an urgent need for Japan to establish and enact a basic act for patient rights. The act should include: respect for a patient's right to self-determination; the right to refuse unwanted treatment; the right to prepare legally binding advance directives; the right to decline to prepare such directives; and access to nationally insured healthcare. It should enable those concerned with patient care involving DT to seek ethical advice from ethics committees. Furthermore, it should state that healthcare professionals involved in the discontinuation of life support in a proper manner are immune to any legal action and that they have the right to conscientiously object to LVAD deactivation.

Background: Cardiac resynchronization therapy is an effective device therapy for heart failure patients with conduction block. However, a problem with this invasive technique is the nearly 30% of non-responders. A number of studies have reported a functional line of block of cardiac excitation propagation in responders. However, this can only be detected using non-contact endocardial mapping. Further, although the line of block is considered a sign of responders to therapy, the mechanism remains unclear. Methods: Herein, we created two patient-specific heart models with conduction block and simulated the propagation of excitation based on a cellmodel of electrophysiology. In one model with a relatively narrow QRS width (176 ms), we modeled the Purkinje network using a thin endocardial layer with rapid conduction. To reproduce a wider QRS complex (200 ms) in the second model, we eliminated the Purkinje network, and we simulated the endocardial mapping by solving the inverse problem according to the actual mapping system. Results: We successfully observed the line of block using non-contact mapping in the model without the rapid propagation of excitation through the Purkinje network, although the excitation in the wall propagated smoothly. This model of slow conduction also reproduced the characteristic properties of the line of block, including dense isochronal lines and fractionated local electrocardiograms. Further, simulation of ventricular pacing from the lateral wall shifted the location of the line of block. By contrast, in the model with the Purkinje network, propagation of excitation in the endocardial map faithfully followed the actual propagation in the wall, without showing the line of block. Finally, switching the mode of propagation between the two models completely reversed these findings. Conclusions: Our simulation data suggest that the absence of rapid propagation of excitation through the Purkinje network is the major cause of the functional line of block recorded by non-contact endocardial mapping. The line of block can be used to identify responders as these patients loose rapid propagation through the Purkinje network.

Background: Medical care is obviously an important public service to ensure the health of a nation; however, medical resources are not always used appropriately. 'Convenience-store consultations' and inappropriate ambulance transportation represent instances of such improper use by contemporary Japanese citizens in recent years. This article illustrates two examples of misuse and discusses potential countermeasures by considering factors contributing to these behaviours., Main Body: From both public and medical perspectives, these patient behaviours are problematic, causing potential harm to others, negative consequences to such patients themselves, exhaustion of healthcare staff, and breakdown of emergency medical services. Although citizens need to recognize the public nature and scarcity of medical care, the more immediate need may be to identify and to remove personal and social causes inducing such misuse. In addition, healthcare professionals should become more trustworthy. To combat these issues, one-sided penalties such as accusations or sanctions for patients who misuse the system cannot be justified in principle. If measures taken to prevent misuse are ineffective, imposing surcharges or restricting consultations may be considered official policy, but these are not acceptable for several reasons., Conclusion: For now, we conclude that we must rely on the spontaneous motivation of patients who engage in 'convenience-store consultations' and ambulance transportation instead of taking a taxi.

Background: The currently proposed criteria for identifying patients who would benefit from cardiac resynchronization therapy (CRT) still need to be optimized. A multi-scale heart simulation capable of reproducing the electrophysiology and mechanics of a beating heart may help resolve this problem. The objective of this retrospective study was to test the capability of patient-specific simulation models to reproduce the response to CRT by applying the latest multi-scale heart simulation technology., Methods and Results: We created patient-specific heart models with realistic three-dimensional morphology based on the clinical data recorded before treatment in nine patients with heart failure and conduction block treated by biventricular pacing. Each model was tailored to reproduce the surface electrocardiogram and hemodynamics of each patient in formats similar to those used in clinical practice, including electrocardiography (ECG), echocardiography, and hemodynamic measurements. We then performed CRT simulation on each heart model according to the actual pacing protocol and compared the results with the clinical data. CRT simulation improved the ECG index and diminished wall motion dyssynchrony in each patient. These results, however, did not correlate with the actual response. The best correlation was obtained between the maximum value of the time derivative of ventricular pressure (dP/dt max ) and the clinically observed improvement in the ejection fraction (EF) (r=0.94, p<0.01)., Conclusions: By integrating the complex pathophysiology of the heart, patient-specific, multi-scale heart simulation could successfully reproduce the response to CRT. With further verification, this technique could be a useful tool in clinical decision making., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A murder case that had some features in common with the Tarasoff case occurred in Sasebo City, Japan, in 2014. A 15-year-old high school girl was murdered and her 16-year-old classmate was arrested on suspicion of homicide. One and a half months before the murder, a psychiatrist who had been examining the girl called a prefectural child consultation centre to warn that she might commit murder, but he did not reveal her name, considering it his professional duty to keep it confidential. Article 134 of the Japanese Criminal Law states that doctors should not disclose patient information obtained in clinical practice without a legitimate reason, but the Japanese Supreme Court has not specified what constitutes a legitimate reason. Mass media and commentators suggested that the murder could have been prevented if the psychiatrist had disclosed the girl's name to the authorities or had isolated her coercively in a psychiatric ward. However, the authors disagree with such claims. This article discusses obligations imposed on concerned individuals and third party members in cases involving ethical dilemmas regarding patient confidentiality and information disclosure. It is concluded that everyone should fulfill their obligations to prevent such tragedies and one should judge the appropriateness of others' actions based not on the consequences of their actions, but on the processes used to decide on a course of action and their commitment. It is necessary for us to establish a society in which concerned parties can do what they think is ethically best without fearing ungrounded charges., (© 2016 John Wiley & Sons Ltd.)

Probiotic Lactobacillus gasseri SBT2055 (LG2055) reduces postprandial TAG absorption and exerts anti-obesity effects in rats and humans; however, the underlying mechanisms are not fully understood. In the present study, we addressed the mechanistic insights of the anti-obesity activity of LG2055 by feeding Sprague-Dawley rats diets containing skimmed milk fermented or not by LG2055 for 4 weeks and by analysing energy expenditure, glucose tolerance, the levels of SCFA in the caecum and serum inflammatory markers. Rats fed the LG2055-containing diet demonstrated significantly higher carbohydrate oxidation in the dark cycle (active phase for rats) compared with the control group, which resulted in a significant increase in energy expenditure. LG2055 significantly reduced cumulative blood glucose levels (AUC) compared with the control diet after 3 weeks and increased the molar ratio of butyrate:total SCFA in the caecum after 4 weeks. Furthermore, the LG2055-supplemented diet significantly reduced the levels of serum amyloid P component - an indicator of the inflammatory process. In conclusion, our results demonstrate that, in addition to the inhibition of dietary TAG absorption reported previously, the intake of probiotic LG2055 enhanced energy expenditure via carbohydrate oxidation, improved glucose tolerance and attenuated inflammation, suggesting multiple additive and/or synergistic actions underlying the anti-obesity effects exerted by LG2055.

The probiotic Lactobacillus gasseri SBT2055 (LG2055) has anti-obesity effects. Obesity is closely correlated with inflammation in adipose tissue, and maintaining adipose tissue in a less-inflamed state requires intestinal integrity or a barrier function to protect the intestine from the disruption that can be caused by a high-fat diet (HFD). Here, we examined the anti-inflammatory and intestinal barrier-protecting effects of LG2055 in C57BL/6 mice fed a normal-fat diet (NFD), HFD, or the HFD containing LG2055 (HFD-LG) for 21 weeks. HFD-LG intake significantly prevented HFD-induced increases in body weight, visceral fat mass, and the ratio of inflammatory-type macrophages to anti-inflammatory ones in adipose tissue. Mice fed the HFD showed higher intestinal permeability to a fluorescent dextran administered by oral administration and an elevated concentration of antibodies specific to lipopolysaccharides (LPS) in the blood compared with those fed the NFD, suggesting an increased penetration of the gut contents into the systemic circulation. These elevations of intestinal permeability and anti-LPS antibody levels were significantly suppressed in mice fed the HFD-LG. Moreover, treatment with LG2055 cells suppressed an increase in the cytokine-induced permeability of Caco-2 cell monolayers. These results suggest that LG2055 improves the intestinal integrity, reducing the entry of inflammatory substances like LPS from the intestine, which may lead to decreased inflammation in adipose tissue.

Administration of Lactobacillus gasseri SBT2055 (LG2055) has been shown to prevent body weight gain and it also down-regulates the expression of the Ccl2 gene in adipose tissue in diet-induced obese mice. The CC chemokine ligand 2 has a crucial role in macrophage infiltration into adipose tissue, which is known to exacerbate inflammation. However, it is not yet known how LG2055 affects the invasion of macrophages into adipose tissue. C57BL/6J male mice were fed a normal-fat diet (10 % energy fat), high-fat diet (HFD; 45 % energy fat), or HFD containing LG2055 for 12 weeks. After the feeding period, gene expression and macrophage population in adipose tissue were analysed by real-time PCR and flow cytometry, respectively. Body weight and abdominal fat weight were not altered by feeding LG2055. Flow cytometry analysis revealed that the population of macrophages in adipose tissue was significantly reduced by feeding LG2055 compared with HFD only. Furthermore, the ratio of classically activated inflammatory macrophages (M1 macrophages) to total macrophages was significantly decreased in the LG2055-fed group. The expressions of Ccl2, Ccr2 and Lep were down-regulated and that of Il6, Tnf and Nos2 tended to be down-regulated in adipose tissue by feeding LG2055. In addition, fasting glucose levels were significantly decreased in the LG2055-fed group. These data suggest that administration of LG2055 might attenuate inflammation, which is caused by the intake of an HFD, through the inhibition of macrophage invasion into adipose tissue.

Background: Lactobacillus gasseri SBT2055 (LG2055) has been shown to prevent abdominal adiposity, and suppression of lipid absorption is considered a possible mechanism, detail of which, however, are poorly understood. In the present study, we evaluated the effects of LG2055 on fat hydrolysis by determining pancreatic lipase activity and fat emulsion properties in vitro. We also examined whether LG2055 influences fecal fat excretion in humans., Methods: Pancreatic lipase activity was investigated in vitro using an artificially prepared fat emulsion and 4-methylumbelliferyl oleate (4-MUO) as substrates. The concentrations of free fatty acids and 4-methylumbelliferone were quantified. Fat emulsion droplet size was measured using a particle size analyzer. The clinical study was performed as a double-blind, randomized, placebo-controlled trial. Subjects consumed 100 g of fermented milk (FM)/d, either with or without LG2055 supplementation, for seven days. Fecal samples were collected during three-day pre-observational and FM intake periods and fecal fat levels were determined., Results: LG2055 dose-dependently suppressed lipase activity in the fat emulsion assay but not in the 4-MUO assay. LG2055 dose-dependently increased fat emulsion droplet size. The effects of LG2055 on lipase activity and fat emulsion properties were increased compared with four other tested strains (Lactobacillus gasseri SBT0317, Lactobacillus gasseri JCM1131T, Lactobacillus. delbrueckii subsp. bulgaricus JCM1002T and Streptococcus thermophilus ATCC19258T). In our clinical study, fecal fat level after FM intake was significantly increased compared with that observed before FM intake in the LG2055-containing active FM group but not the control FM group lacking LG2055., Conclusions: LG2055 increased fat emulsion droplet size, resulting in the suppression of lipase-mediated fat hydrolysis. The influence of LG2055 on the physicochemical properties of fat emulsion provides a mechanism for the probiotic-mediated suppression of lipid absorption and promotion of fecal fat excretion in humans., Trial Registration: UMIN000015772.

Lactobacillus helveticus SBT2171 (LH2171) is a lactic acid bacterium with high protease activity and used in starter cultures in the manufacture of cheese. We recently reported that consumption of cheese manufactured using LH2171 alleviated symptoms of dextran sodium sulfate (DSS)-induced colitis in mice. In this study, we have examined whether LH2171 itself exerts an inhibitory effect on the excessive proliferation of lymphocytes. We found that LH2171 inhibited the proliferation of LPS-stimulated mouse T and B cells, and the human lymphoma cell lines, Jurkat and BJAB. Cell cycle analysis showed an accumulation of LH2171-treated BJAB cells in the G2/M phase. Further, phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun was reduced by LH2171 in BJAB cells. Subsequently, expression of cell division cycle 2 (CDC2), regulated by the JNK signaling pathway and essential for G2/M phase progression, was inhibited by LH2171. It was also demonstrated that intraperitoneal administration of LH2171 strongly alleviated symptoms of collagen-induced arthritis (CIA) in mice. These findings suggest that LH2171 inhibits the proliferation of lymphocytes through a suppression of the JNK signaling pathway and exerts an immunosuppressive effect in vivo.

Probiotic bacteria provide benefits in enhancing host immune responses and protecting against infection. Induction of IgA production by oral administration of probiotic bacteria in the intestine has been considered to be one reason for this beneficial effect, but the mechanisms of the effect are poorly understood. Lactobacillus gasseri SBT2055 (LG2055) is a probiotic bacterium with properties such as bile tolerance, ability to improve the intestinal environment, and it has preventive effects related to abdominal adiposity. In this study, we have found that oral administration of LG2055 induced IgA production and increased the rate of IgA(+) cell population in Peyer's patch and in the lamina propria of the mouse small intestine. The LG2055 markedly increased the amount of IgA in a co-culture of B cells and bone marrow derived dendritic cells (BMDC), and TLR2 signal is critical for it. In addition, it is demonstrated that LG2055 stimulates BMDC to promote the production of TGF-β, BAFF, IL-6, and IL-10, all critical for IgA production from B cells. Combined stimulation of B cells with BAFF and LG2055 enhanced the induction of IgA production. Further, TGF-β signal was shown to be critical for LG2055-induced IgA production in the B cell and BMDC co-culture system, but TGF-β did not induce IgA production in a culture of only B cells stimulated with LG2055. Furthermore, TGF-β was critical for the production of BAFF, IL-6, IL-10, and TGF-β itself from LG2055-stimulated BMDC. These results demonstrate that TGF-β was produced by BMDC stimulated with LG2055 and it has an autocrine/paracrine function essential for BMDC to induce the production of BAFF, IL-6, and IL-10.

Background: Healthcare professionals must make decisions for patients based on ethical considerations. However, they rely on clinical ethics consultations (CEC) to review ethical justifications of their decisions. CEC consultants support the cases reviewed and guide medical care. When both healthcare professionals and CEC consultants face ethical problems in medical care, how is their judgment derived? How do medical judgments differ from the ethical considerations of CECs? This study examines CECs in Japan to identify differences in the ethical judgment of clients and CEC consultants., Methods: The CEC request and response documents of all 60 cases reviewed across Japan between October 2006 and the end of October 2011 were classified in terms of the presence of decisional capacity in the patient. We conducted a qualitative content analysis of the differences in reasoning between client and CEC consultants. Reasoned judgments were verified in individual cases to classify the similarities or differences of opinion between CEC clients and teams., Results: As the result of classification of the decisional capacity and the difference of opinion regarding medical care, the most frequent category was 25 cases (41.7%) of "uncertain decisional capacity," and 23 cases (38.3%) of "withholding of decision-making." A chi-square analysis was performed on presence of decisional capacity and agreement in decision-making, yielding a statistically significant difference (p < 0.05). The CEC consultants' reasoning was based on "patient's preference was ambiguous," "validity of family as a surrogate," "estimation of patient preference," and "patient's best interest," whereas the CEC client's reasoning was based on "consistent family preference was shown/not shown" and "appropriate therapeutic methods to manage patient safety.", Conclusion: Differences in opinions were found in cases classified according to decisional capacity. Furthermore, the reasoning behind judgments differed between CEC clients and CEC consultants. The reasoning of CEC consultants was critical and reflective, while for clients it was situational and pragmatic.

Background: Lactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals., Methods: We conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured., Results: The OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period., Conclusions: The consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus., Trial Registration: UMIN000011605.

In the issue of futile treatments, patients and healthcare professionals tend to disagree. We conducted an Internet questionnaire survey and explored the Japanese nurses' attitude toward this topic, comparing with that of laypeople. In total, 522 nurses and 1134 laypeople completed the questionnaire. Nurse respondents were significantly less in favor of providing potentially futile treatments in hypothetical vignettes and stressed quality of life of the patient for judging the futility of a certain treatment. Of them, 85.4% reported having experienced providing such treatments. Reasons for providing them included factors related to not only patients but also healthcare teams. Our results indicate that attitudes among Japanese nurses toward the issue of futile treatments are different from patients and that their actual practice is influenced by several situational factors.

Purpose: Probiotic Lactobacillus gasseri SBT2055 (LG2055) has an anti-obesity effect although it is unknown whether the effect influences inflammatory responses in adipose tissue and lipid metabolism in the liver, which are considered substantially relevant to adiposity., Methods: C57BL/6 mice were fed a 10%-fat diet containing LG2055 cells for 24 weeks. We then studied body weight, fat tissue mass, liver fat content and inflammatory genes in the adipose tissue, and lipogenic and lipolytic genes in the liver., Results: Consumption of LG2055 resulted in a significant reduction in body weight and fat tissue mass (epididymal and perirenal/retroperitoneal), with a lowered level of triglyceride content in the liver. DNA microarray analysis showed that LG2055 generally inhibited the up-regulation of pro-inflammatory genes, including CCL2 and CCR2, in the epididymal adipose tissue. In the liver, LG2055 tended to inhibit lipogenic gene up-regulation, including ACC1, FAS and SREBP1, but LG2055 did not markedly alter lipolytic genes. Real-time PCR analysis confirmed the DNA microarray results in part, showing a significant reduction in the mRNA expression of CCL2 in the epididymal adipose tissue, and a downward tendency in FAS mRNA expression in the liver, in the LG2055-fed group., Conclusions: LG2055 significantly prevented body weight gain, fat accumulation and pro-inflammatory gene expression in the adipose tissue. Relatively lower triglyceride levels and reduced expression of lipogenic genes were also observed in the liver. It is suggested that improvement in the inflammatory state of the adipose tissue might be a possible mechanism underlying the anti-obesity effect of LG2055.

Consumption of fermented milk (FM) containing a probiotic, Lactobacillus gasseri SBT2055 (LG2055), previously showed a reduction in abdominal adiposity in a randomised controlled trial (RCT) using FM with 10(8) colony-forming units (cfu) of LG2055/g. However, whether the effectiveness is observed at lower concentrations, the recommended minimum or intermediate levels of probiotics (10(6) or 10(7) cfu/g, respectively), remains to be examined. A multi-centre, double-blind, parallel-group RCT was conducted using 210 healthy Japanese adults with large visceral fat areas (80·2 - 187·8 cm(2)). They were balanced for their baseline characteristics and randomly assigned to three groups receiving FM containing 10(7), 10(6) or 0 (control) cfu LG2055/g of FM, and were asked to consume 200 g FM/d for 12 weeks. Abdominal visceral fat areas, which were determined by computed tomography, at week 12, changed from baseline by an average of -8·5 % (95 % CI -11·9, -5·1; P< 0·01) in the 10(7) dose group, and by -8·2 % (95 % CI -10·8, -5·7; P< 0·01) in the 10(6) dose group. Other measures including BMI, waist and hip circumferences, and body fat mass were also significantly decreased from baseline at week 12 in both groups; interestingly, the cessation of taking FM for 4 weeks attenuated these effects. In the control group, none of these parameters significantly decreased from baseline. These findings demonstrate that consumption of LG2055 at doses as low as the order of 10(8) cfu/d exhibited a significant lowering effect on abdominal adiposity, and suggest that constant consumption might be needed to maintain the effect.

A placebo is a substance or intervention believed to be inactive, but is administered by the healthcare professional as if it was an active medication. Unlike standard treatments, clinical use of placebo usually involves deception and is therefore ethically problematic. Our attitudes toward the clinical use of placebo, which inevitably includes deception or withholding information, have a tremendous effect on our practice regarding truth-telling and informed consent. A casual attitude towards it weakens the current practice based on shared decision-making and mutual trust between patients and healthcare professionals. Issues concerning the clinical use of placebo are thus intimately related to patient-provider relationships, the public's trust in medicine, and medical education. A review of recent survey studies suggests that the clinical use of placebo appears to be fairly well accepted among healthcare professionals and is common in clinical settings in various countries. However, we think that an ethical discussion is urgently needed because of its controversial nature. If judged to be ethically wrong, the practice should end. In the present paper, we discuss the ethicality of the clinical use of placebo with deception and argue against it, concluding that it is unethical and should be banned. We will show that most arguments in favor of the clinical use of placebo can be refuted and are therefore incorrect or weak. These arguments will be presented and examined individually. Finally, we will briefly consider issues relevant to the clinical use of placebo without deception., (© 2012 Blackwell Publishing Ltd.)

Background: Recent studies, supported by advances in computer science, have successfully simulated the excitation and repolarization processes of the heart, based on detailed cell models of electrophysiology and implemented with realistic morphology., Methods: In this study, we extend these approaches to simulate the body surface electrocardiogram (ECG) of specific individuals. Patient-specific finite element models of the heart and torso are created for four patients with various heart diseases, based on clinical data including computer tomography, while the parallel multi-grid method is used to solve the dynamic bi-domain problem. Personalization procedures include demarcation of nonexcitable tissue, allocation of the failing myocyte model of electrophysiology, and modification of the excitation sequence. In particular, the adjustment of QRS morphology requires iterative computations, facilitated by the simultaneous visualization of the propagation of excitation in the heart, average QRS vector in the torso, and 12-lead ECG., Results: In all four cases we obtained reasonable agreement between the simulated and actual ECGs. Furthermore, we also simulated the ECGs of three of the patients under bi-ventricular pacing, and once again successfully reproduced the actual ECG morphologies. Since no further adjustments were made to the heart models in the pacing simulations, the good agreement provides strong support for the validity of the models., Conclusions: These results not only help us understand the cellular basis of the body surface ECG, but also open the possibility of heart simulation for clinical applications., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

The year 2010 marked the centenary of the birth of Akira Kurosawa (1910-1998), whose works have been reassessed favourably in the last couple of years in Japan. During his lifetime, Kurosawa directed and produced three films whose chief characters are medical doctors: Drunken Angel (1948), The Quiet Duel (1949) and Red Beard (1965). This paper discusses these three films and examines the thoughts and lives of the three protagonists from the perspective of modern medical ethics. The films depict contemporary ethical and social problems, and deal with paternalism, a healthy professional life and the proper place for human reason in medicine, all of which still give rise to debate in modern medical settings. They are very impressive in their portrayal of extreme paternalism, excessively professional lives and disproportionate reliance on rationality. The doctors are role models in certain situations and are examples of how not to behave in other situations. On the one hand, they are devoted to helping their patients, with their self-sacrifice firmly based on humanity and medical ethics. On the other hand, they perform unwelcome favours and are unhealthy role models who might harm others through narrow-minded attitudes about human beings, a fixed view of life and inflexible ideas about medicine. In this sense, they can be regarded as a rather mixed blessing. These films provide us with an opportunity to simultaneously recognise the importance of modern ethical principles and the significance of 'old' ethical values.

As of 2009, the number of donors in Japan is the lowest among developed countries. On July 13, 2009, Japan's Organ Transplant Law was revised for the first time in 12 years. The revised and old laws differ greatly on four primary points: the definition of death, age requirements for donors, requirements for brain-death determination and organ extraction, and the appropriateness of priority transplants for relatives. In the four months of deliberations in the National Diet before the new law was established, various arguments regarding brain death and organ transplantation were offered. An amazing variety of opinions continue to be offered, even after more than 40 years have elapsed since the first heart organ transplant in Japan. Some are of the opinion that with the passage of the revised law, Japan will finally become capable of performing transplants according to global standards. Contrarily, there are assertions that organ transplants from brain-dead donors are unacceptable because they result in organs being taken from living human beings. Considering the current conditions, we will organize and introduce the arguments for and against organ transplants from brain-dead donors in contemporary Japan. Subsequently, we will discuss the primary arguments against organ transplants from brain-dead donors from the perspective of contemporary Japanese views on life and death. After introducing the recent view that brain death should not be regarded as equivalent to the death of a human being, we would like to probe the deeply-rooted views on life and death upon which it is based., (© 2010 Blackwell Publishing Ltd.)

Background: Empirical surveys about medical futility are scarce relative to its theoretical assumptions. We aimed to evaluate the difference of attitudes between laypeople and physicians towards the issue., Methods: A questionnaire survey was designed. Japanese laypeople (via Internet) and physicians with various specialties (via paper-and-pencil questionnaire) were asked about whether they would provide potentially futile treatments for end-of-life patients in vignettes, important factors for judging a certain treatment futile, and threshold of quantitative futility which reflects the numerical probability that an act will produce the desired physiological effect. Also, the physicians were asked about their practical frequency and important reasons for futile treatments., Results: 1134 laypeople and 401 (80%) physicians responded. In all vignettes, the laypeople were more affirmative in providing treatments in question significantly. As the factors for judging futility, medical information and quality of life (QOL) of the patient were rather stressed by the physicians. Treatment wish of the family of the patient and psychological impact on patient side due to the treatment were rather stressed by laypeople. There were wide variations in the threshold of judging quantitative futility in both groups. 88.3% of the physicians had practical experience of providing futile treatment. Important reasons for it were communication problem with patient side and lack of systems regarding futility or foregoing such treatment., Conclusion: Laypeople are more supportive of providing potentially futile treatments than physicians. The difference is explained by the importance of medical information, the patient family's influence to decision-making and QOL of the patient. The threshold of qualitative futility is suggested to be arbitrary.

We have demonstrated previously that a diet containing skimmed milk (SM) fermented by Lactobacillus gasseri SBT2055 (LGSP) reduces adipocyte size in Sprague-Dawley rats. Two experiments were conducted to extend these observations in order to elucidate the mechanism involved. In experiment 1, lean and obese Zucker rats were fed a diet containing SM or LGSP for 4 weeks. The LGSP diet, compared with the SM diet, resulted in lowering of the mesenteric adipose tissue weight (23 %; P < 0.05), adipocyte sizes (28 %; P < 0.001) and serum leptin concentration (36 %; P < 0.05) in lean rats. Obese Zucker rats did not display such dietary effects. Only the number of smaller adipocytes was increased (P < 0.05) by the LGSP diet in the subcutaneous adipose tissue of obese rats. The LGSP diet significantly reduced the serum and hepatic cholesterol in rats. In addition, the LGSP diet led to an increased excretion of faecal fatty acids and total neutral faecal sterols in both rat strains. In experiment 2, Sprague-Dawley rats with permanent cannulation of the thoracic duct were fed either the SM or LGSP diets and their lymph was collected. The LGSP diet lowered the maximum transport rate of TAG and phospholipids. These results indicate that fermented milk regulates adipose tissue growth through inhibition at the stage of dietary fat absorption in lean Zucker rats.

Recent advances in biotechnology and the availability of ever more powerful computers have led to the formulation of increasingly complex models at all levels of biology. One of the main aims of systems biology is to couple these together to produce integrated models across multiple spatial scales and physical processes. In this review, we formulate a definition of multi-scale in terms of levels of biological organisation and describe the types of model that are found at each level. Key issues that arise in trying to formulate and solve multi-scale and multi-physics models are considered and examples of how these issues have been addressed are given for two of the more mature fields in computational biology: the molecular dynamics of ion channels and cardiac modelling. As even more complex models are developed over the coming few years, it will be necessary to develop new methods to model them (in particular in coupling across the interface between stochastic and deterministic processes) and new techniques will be required to compute their solutions efficiently on massively parallel computers. We outline how we envisage these developments occurring.

A 20-year-old woman was admitted to another hospital due to schizophrenia in July 2003. The patient felt chest pain and palpitation in August, and she was referred to our hospital. Chest computed tomography (CT) showed a mass in the left thoracic cavity and a pleural/pericardial effusion. Since general condition did not improved in spite of aggressive supportive treatment, surgical treatment was chosen. An operation was performed via median sternotomy in September. The tumor was found to have adhered firmly to the surrounding organs. Pericardial fenestration was performed; then the tumor was resected with the left phrenic nerve due to tight adhesion. The patient received respiratory support in the intensive care unit for 5 days after surgery, uneventfully. Twenty-three months after surgery, she is surviving and free from schizophrenic symptoms without medication.

On February 25, 2004, 59-year-old woman visited a local clinic due to lower abdominal pain. On February 28, she was admitted to the clinic due to severe abdominal pain. Computed tomography (CT) showed a mass in the lower abdomen and plural effusion and athelectasis of the right lung. She had severe anemia (Hb 6.9 g/dl). On March 1, she was transferred to our hospital. Pleural fluid was revealed to be sanguineous by thoracentasis. She underwent thoracotomy on the day of admission. There was no source of bleeding in the pleural space. A small pore, 3 mm in diameter, was found in the tendinous portion of the diaphragm. An influx of bloody fluid from the abdomen via the pore caused hemothorax. Laparotomy was performed, followed by closure of the pore using direct suture. The origin of the abdominal bleeding was pedicle torsion of the right ovarian tumor. Seven months after surgery she was uneventful with no pleural effusion.

Background: In measuring specific IgE levels in sera by direct ELISA, competition with coexisting IgG often impedes an exact IgE determination; additionally, IgG autoantibodies to IgE (IgG-IgE) in sera affect the assay. In this paper, we attempt to determine accurate specific IgE levels by selective removal of IgG with a protein G-immobilized gel (PG) and by acid treatment of the PG to compensate for the unintended removal of IgE, probably due to the PG binding IgG-IgE., Methods: IgG in sera was removed using PG at pH 7.0. Then, the PG was treated with citrate buffer at pH 3.0 for 5 min to liberate IgE from IgG-IgE complexes, after IgG-binding sites on the PG were saturated with bovine IgG, since PG came to bind IgE at acidic pHs. IgE levels were then measured by ELISA., Results: The PG treatment of sera removed the effect of inhibitory competition by coexisting IgG, especially at higher concentrations of sera, to improve specific IgE detection by direct ELISA. However, PG treatment alone sometimes reduced IgE levels (39% of sera tested), even though PG does not bind IgE at pH 7.0, which indicated the presence of IgG-IgE complexes. The reduction in IgE returned almost to their original levels in the sera by acid treatment of the PG. By combining the PG treatment with acid treatment, specific IgE measurement in sera was improved significantly (p < 0.01, Wilcoxon signed rank test)., Conclusion: Measurement of specific IgE in sera by direct ELISA was improved by using the PG and acid treatment technique., (Copyright 2000 S. Karger AG, Basel.)