Published papers

Non-alcoholic steatohepatitis (NASH) is a progressive disease that occurs in the liver. As the number of people with NASH has increased, effective prevention and treatment strategies are needed. Agaricus brasiliensis KA21 (AGA) is a mushroom native to Brazil and is considered a healthy food because of its purported health benefits, including its antioxidant properties. In this study, we focused on the oxidative stress that accompanies the onset of NASH and examined whether AGA can prevent NASH development through its antioxidant activity. We used a mouse model of NASH in which pathogenesis was promoted by dietary induction. Supplementation with AGA attenuated the development of hepatic fibrosis, which is a characteristic feature of late-stage NASH. This effect appeared to be mechanistically linked to an AGA-promoted reduction in hepatic oxidative stress. These results demonstrate a novel role for AGA in NASH prevention.

Human Metabolism; Microbiome

We aimed to obtain greater understanding of dentists' distress when they diagnose and treat patients with temporomandibular disorders (TMD), and to explore ways in which TMD can be better treated. We conducted a cross-sectional study based on a questionnaire survey of dentists (n = 148). Dentists were queried using an open-ended questionnaire about distress they experienced when treating patients with TMD. Survey responses were analyzed using mixed methods. Associations between specific dentist and patient characteristics and types of distress were analyzed by one way analysis of variance and residual analysis. One hundred thirteen clinicians responded to the questionnaire, giving a 76% response rate. Thematic analysis identified 6 major themes: difficulty in predicting therapeutic effect and prognosis; difficulty in diagnosis; difficulty in the decision about whether to do occlusal adjustment; difficulty in specifying a cause; difficulty in communicating with patients and mental factors; and health insurance system barriers. Clinicians who reported difficulty in deciding whether to do occlusal adjustment saw significantly more patients who experienced shoulder stiffness and headache (P = .008 and P = .022, respectively). Dentists' knowledge of TMD guidelines was associated with a lower percentage of difficulty in predicting therapeutic effect and prognosis (residual analysis; P = .010). These findings provide important insights into clinician's perception of difficulties with patients experiencing TMD-related pain. Knowledge of the existence of TMD clinical practice guidelines may lower dentist distress, particularly with regard to prognosis. Further studies are needed to decrease dentist's distress and to overcome the evidence-practice gap in TMD treatment.

Objectives: This study quantified and compared practice patterns of treatment for deep occlusal carious lesions among Japanese dentists, and tested the hypothesis that dentist characteristics are significantly associated with the decision to choose an indirect pulp capping (IPC), a form of selective carious tissue removal that involves leaving a thin layer of demineralized tissue over the pulp, that is then covered with a protective liner. Methods: This cross-sectional study was conducted using a questionnaire survey of dentists affiliated with the Dental Practice-based Research Network Japan (n = 297). Dentists were asked to indicate what percentage of time they use three treatment options when treating patients with deep occlusal caries and possible mild pulpitis on a posterior tooth. Response options were “1. Stop before removing all caries and perform an IPC”, “2. Remove all caries and proceed with a direct pulp cap”, and “3. Remove all caries and proceed with endodontic-related procedures”. Percentages of options 1–3 were compared by multiple comparison. Associations between dentist characteristics and a higher percentage of IPC provision (option 1) were analyzed via logistic regression. Results: Responses were obtained from 206 dentists. Median percentages (interquartile ranges) of options 1, 2 and 3 were 30% (10–59%), 10% (0–30%), and 40% (19–80%), respectively. The differences between option 3 and options 1 and 2 were significant (p < 0.001). In logistic regression analysis, a higher frequency of obtaining evidence from English-language scientific articles was significantly associated with a higher percentage of IPC, with an odds ratio of 2.28 (95%CI: 1.14–4.54). Conclusions: Endodontic-related procedures remain the most frequent treatment option for deep occlusal caries. Frequent use of evidence-based information in English-language scientific articles was associated with Japanese dentists’ preference toward IPC. Clinical Significance: Japanese dentists would most frequently choose endodontic-related procedures, followed by IPC and direct pulp capping for treatment of patients with deep occlusal caries with possible mild pulpitis on posterior teeth. Significant association was identified between use of evidence-based information in the English-language scientific literature and Japanese dentists’ preference for IPC.

Objectives: This study aimed to 1) quantify the evidence-practice gap (EPG) between dental clinical practice and published evidence on Minimal Intervention Dentistry (MID) among dentists in Japan; and 2) examine the hypothesis that dentist characteristics have a significant association with the EPG. Methods: We conducted a cross-sectional study via use of a web-based questionnaire survey of dentists who were affiliated with the Dental Practice-based Research Network Japan (n = 297). To quantify the EPG on MID, we used a questionnaire that included 10 clinical questions or scenarios to assess concordance between dental practice and published evidence on MID. We evaluated concordance by coding responses to each question as consistent or inconsistent with the evidence. An overall concordance was then determined as percent of responses that were consistent with published evidence for 10 questions. Subsequently, multiple logistic regression analysis was conducted to examine the associations between dentist characteristics and higher overall concordance (≥median) with published evidence. Results: Mean and median overall dentist-level concordance were both 60 % (SD: 18, interquartile range: 50–75 %). Logistic regression analysis showed that “gender of dentist”, “city population”, and “frequency of obtaining evidence from the scientific journal articles in English” were significantly associated with high concordance, with odds ratios (95 % CIs) of 2.33 (1.01–5.39), 2.01 (1.02–3.96), and 2.45 (1.08–5.59), respectively. Conclusions: Japanese dentists demonstrated medium concordance with published evidence, indicating that an EPG on MID exists in Japanese dental clinical practices. Dentist-specific characteristics had significant associations with high concordance with published evidence. Clinical Significance: Despite the establishment and dissemination of the concept of MID, the EPG on MID exists in Japanese dental clinical practices. A high concordance was significantly associated with the following dentist characteristics: “female dentist”, “dental clinic location in a government-ordinance-designated city”, and “frequently obtaining evidence from the English-language scientific journal articles”

A high-calorie diet causes fat accumulation and oxidative stress in the liver, leading to fatty liver and eventually non-alcoholic steatohepatitis (NASH). Melon GliSODin® is used as a nutritional supplement because of its antioxidant activity. This study aimed to assess the antioxidant activity of Melon GliSODin® and its effectiveness in preventing NASH, which primarily results from oxidative stress. Furthermore, we verified the protective effect of Melon GliSODin® by administering it to a mouse model of diet-induced NASH. Melon GliSODin® suppressed liver fibrosis and fat accumulation, which is characteristic of the NASH phenotype. Gene expression analysis confirmed the suppression of fat synthesis and activation of antioxidative mechanisms. These results show that Melon GliSODin® mitigates NASH onset at the molecular level, suggesting its potential application as a NASH preventive agent.

Objectives: This study aimed to identify (i) which practice-based research agendas had the highest priority among patients and (ii) whether priorities varied significantly with patient age and gender. Methods: We conducted a cross-sectional questionnaire survey of 482 patients from 11 outpatient dental practices. The patients were shown 31 items concerning practice-based research questions and asked to select the three items in which they were most interested. We generated a rank order of the 31 items. Subsequently, the 31 items were categorised into 10 groups, and we performed subgroup analyses according to age and gender using chi-square tests. Results: “Age-specific care to maintain oral health (n = 86)” was rated as the most interesting research question. When data were analysed according to age, patients less than 40 years old rated “Orthodontic treatment”, “Esthetic dental care” and “Topical fluoride application” as interesting questions significantly more frequently than did patients 40 years old or older (P < 0.01)?, while patients 40 years old or older rated “Regular dental check-ups”, “Dental implant”, “Diet and food” and “Social health insurance” as more interesting than did patients less than 40 years old (P < 0.05). When data were analysed according to gender, female patients rated the questions on aesthetic dental care as more interesting than did male patients (P < 0.01), whereas male patients rated questions on toothbrushing as more interesting than did female patients (P < 0.05). Conclusions: Patients assessed “Age-specific care to maintain oral health” as the highest priority among a broad range of research topics. This study also quantified patient priorities for research agendas according to age and gender group. Designing future research with these priorities in mind will promote patient-centred evidence.

While brown adipose tissue (BAT) is well-recognized for its ability to dissipate energy in the form of heat, recent studies suggest multifaced roles of BAT in the regulation of glucose and lipid homeostasis beyond stimulating thermogenesis. One of the functions involves interorgan communication with metabolic organs, such as the liver, through BAT-derived secretory factors, a.k.a., batokine. However, the identity and the roles of such mediators remain insufficiently understood. Here, we employed proteomics and transcriptomics in human thermogenic adipocytes and identified previously unappreciated batokines, including phospholipid transfer protein (PLTP). We found that increased circulating levels of PLTP, via systemic or BAT-specific overexpression, significantly improve glucose tolerance and insulin sensitivity, increased energy expenditure, and decrease the circulating levels of cholesterol, phospholipids, and sphingolipids. Such changes were accompanied by increased bile acids in the circulation, which in turn enhances glucose uptake and thermogenesis in BAT. Our data suggest that PLTP is a batokine that contributes to the regulation of systemic glucose and lipid homeostasis as a mediator of BAT-liver interorgan communication.