Details of a Researcher - Yokoyama, Yoko

Papers - Yokoyama, Yoko

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Sodium ferrous citrate and 5-aminolevulinic acid improve type 2 diabetes by maintaining muscle and mitochondrial health.

Kitamura N, Zhang S, Morel JD, Nagano U, Taworntawat T, Hosoda S, Nakamura A, Ogawa Y, Benegiamo G, Auwerx J, Tsubota K, Yokoyama Y, Watanabe M

Obesity (Silver Spring, Md.) 2023.02

ISSN 1930-7381

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Web-based intervention to improve the evidence-practice gap in minimal intervention dentistry: Findings from a dental practice-based research network

Kakudate N., Yokoyama Y., Sumida F., Matsumoto Y., Takata T., Gordan V.V., Gilbert G.H.

Journal of Dentistry (Journal of Dentistry) 115 103854 2021.12

ISSN 03005712

Objectives: To determine whether: the evidence-practice gap (EPG) in minimal intervention dentistry (MID) can be improved by a tailored web-based intervention, and specific clinical situations might impede implementing MID. Methods: We conducted a before-after intervention study and a qualitative study. Two web-based questionnaire surveys were conducted among 197 Japanese dentists. In the first questionnaire, a baseline EPG was measured using six questionnaire items. Subsequently, feedback material about the EPG was electronically prepared, including results of the first questionnaire, international comparisons with a previous study from the US, and a summary of recent evidence on MID. In the second questionnaire, the EPG was re-measured after participants read the material. The primary outcome was mean overall concordance between published evidence and the dentist's clinical practice for all six questions. During the second questionnaire, we performed qualitative content analysis using free-text responses to a question about difficult situations encountered when conducting MID. Results: Regarding before and after comparisons of concordance between the first and second questionnaires, mean overall concordance improved significantly, from 66% to 89% (p<0.001). Qualitative content analysis identified five difficult situations: “cases where decision making for treatment and prognosis is difficult”, “inadequate practice resources”, “limitations on patient visit and treatment period”, “discrepancy between MID and the patient's values”, and “limitations on health insurance and social understanding”. Conclusions: These results suggest that it is possible to reduce the EPG in MID using a web-based educational intervention among Japanese dentists. Qualitative content analysis revealed five difficult situations that might hinder implementation of MID. Clinical Significance: Although this intervention demonstrated educational effects, perfect concordance was not achieved by all participants. This is possibly associated with the five situations that participants reported facing when conducting MID. Creating an environment to improve these situations may facilitate a reduction in the EPG.

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Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways

Kitamura N., Yokoyama Y., Taoka H., Nagano U., Hosoda S., Taworntawat T., Nakamura A., Ogawa Y., Tsubota K., Watanabe M.

Scientific Reports (Scientific Reports) 11 ( 1 ) 10753 2021.12

ISSN 2045-2322

Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron–sulfur (Fe–S) cluster synthesis. Heme and Fe–S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.

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Metabolic effects of bee larva-derived protein in mice: Assessment of an alternative protein source

Yokoyama Y., Shinohara K., Kitamura N., Nakamura A., Onoue A., Tanaka K., Hirayama A., Aw W., Nakamura S., Ogawa Y., Fukuda S., Tsubota K., Watanabe M.

Foods (Foods) 10 ( 11 ) 2021.11

ISSN 2304-8158

Food crises caused by growing global population or environmental changes are predicted in the near future; therefore, sustainable solutions are needed. Edible insects, which are rich in protein and can save feed and environmental resources, have the potential to be a sustainable alternative protein source. However, there is limited evidence on the impact on health. In this study, we investigated the biological effects of ingesting bee larva by examining their effects on amino acid, lipid, and glucose metabolism in animal models. In our animal experiments, the replacement of casein as a protein source, with edible insects, did not seem to cause any deficiency in murine amino acid levels in the plasma and liver. Metabolomic analysis of plasma metabolites showed decreased 3-methylhistidine and increased nicotinamide in the bee larva-derived protein-fed mice. Decreased levels of plasma 3-metylhistidine, an indicator of muscle degradation, implies that replacement to bee-larva protein from casein did not cause muscle degradation in vivo. We further investigated effects of increased plasma nicotinamide on peripheral tissue and found an increase in expression levels of genes involved in glucose uptake in muscle and thermogenesis in adipose tissue. These data imply that bee larva is a potential sustainable, safe and healthy alternative protein source.

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Evidence-practice gap in minimal intervention dentistry: Findings from a dental practice-based research network

Kakudate N., Yokoyama Y., Sumida F., Matsumoto Y., Yamazaki H., Touge T., Fujikawa Y., Gordan V.V., Gilbert G.H.

Journal of Dentistry (Journal of Dentistry) 102 103469 2020.11

ISSN 03005712

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”

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Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

Nakamura A., Yokoyama Y., Tanaka K., Benegiamo G., Hirayama A., Zhu Q., Kitamura N., Sugizaki T., Morimoto K., Itoh H., Fukuda S., Auwerx J., Tsubota K., Watanabe M.

iScience (iScience) 23 ( 9 ) 101522 2020.09

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The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT–liver communication

Sponton C.H., Hosono T., Taura J., Jedrychowski M.P., Yoneshiro T., Wang Q., Takahashi M., Matsui Y., Ikeda K., Oguri Y., Tajima K., Shinoda K., Pradhan R.N., Chen Y., Brown Z., Roberts L.S., Ward C.C., Taoka H., Yokoyama Y., Watanabe M., Karasawa H., Nomura D.K., Kajimura S.

EMBO Reports (EMBO Reports) 21 ( 9 ) e49828 2020.09

ISSN 1469221X

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.

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A high-salt/high fat diet alters circadian locomotor activity and glucocorticoid synthesis in mice

Yokoyama Y., Nakamura T.J., Yoshimoto K., Ijyuin H., Tachikawa N., Oda H., Shiraishi R., Shinohara K., Kumadaki K., Honda S., Nakamura A., Kitamura N., Tsubota K., Watanabe M.

PLoS ONE (PLoS ONE) 15 ( 5 ) e0233386 2020.05

ISSN 1932-6203

Salt is an essential nutrient; however, excessive salt intake is a prominent public health concern worldwide. Various physiological functions are associated with circadian rhythms, and disruption of circadian rhythms is a prominent risk factor for cardiovascular diseases, cancer, and immune disease. Certain nutrients are vital regulators of peripheral circadian clocks. However, the role of a high-fat and high-salt (HFS) diet in the regulation of circadian gene expression is unclear. This study aimed to investigate the effect of an HFS diet on rhythms of locomotor activity, caecum glucocorticoid secretion, and clock gene expression in mice. Mice administered an HFS diet displayed reduced locomotor activity under normal light/dark and constant dark conditions in comparison with those administered a normal diet. The diurnal rhythm of caecum glucocorticoid secretion and the expression levels of glucocorticoid-related genes and clock genes in the adrenal gland were disrupted with an HFS diet. These results suggest that an HFS diet alters locomotor activity, disrupts circadian rhythms of glucocorticoid secretion, and downregulates peripheral adrenal gland circadian clock genes.

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Melon GliSODin® prevents diet-induced NASH onset by reducing fat synthesis and improving liver function

Nakamura A., Kitamura N., Yokoyama Y., Uchida S., Kumadaki K., Tsubota K., Watanabe M.

Nutrients (Nutrients) 11 ( 8 ) 2019.08

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.

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Practice-based research agenda priorities selected by patients: findings from a dental practice-based research network

Kakudate N., Yokoyama Y., Sumida F., Matsumoto Y., Riley J.L., Gordan V.V., Gilbert G.H.

International Dental Journal (International Dental Journal) 69 ( 3 ) 183 - 191 2019.06

ISSN 00206539

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.

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Dentists’ practice patterns of treatment for deep occlusal caries: Findings from a dental practice-based research network

Kakudate N., Yokoyama Y., Sumida F., Matsumoto Y., Gordan V.V., Gilbert G.H.

Journal of Dentistry (Journal of Dentistry) 84 76 - 80 2019.05

ISSN 03005712

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.

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Agaricus brasiliensis KA21 May Prevent Diet-Induced Nash through Its Antioxidant, Anti-Inflammatory, and Anti-Fibrotic Activities in the Liver

Nakamura A., Zhu Q., Yokoyama Y., Kitamura N., Uchida S., Kumadaki K., Tsubota K., Watanabe M.

Foods (Foods) 8 ( 11 ) 2019

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.

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Dentist's distress in the management of chronic pain control

Yokoyama Y., Kakudate N., Sumida F., Matsumoto Y., Gordan V.V., Gilbert G.H.

Medicine (United States) (Medicine (United States)) 97 ( 1 ) e9553 2018.01

ISSN 00257974

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.

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Association between plant-based diets and plasma lipids: a systematic review and meta-analysis.

Yokoyama Y, Levin SM, Barnard ND

Nutrition reviews 75 ( 9 ) 683 - 698 2017.09

ISSN 0029-6643

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Use of clinical practice guidelines by dentists: findings from the Japanese dental practice-based research network.

Kakudate N, Yokoyama Y, Sumida F, Matsumoto Y, Gordan VV, Gilbert GH

Journal of evaluation in clinical practice 23 ( 1 ) 96 - 101 2017.02

ISSN 1356-1294

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Vegetarian diets and glycemic control in diabetes: a systematic review and meta-analysis.

Yokoyama Y, Barnard ND, Levin SM, Watanabe M

Cardiovascular diagnosis and therapy 4 ( 5 ) 373 - 82 2014.10

ISSN 2223-3652

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Vegetarian diets and blood pressure: a meta-analysis.

Yokoyama Y, Nishimura K, Barnard ND, Takegami M, Watanabe M, Sekikawa A, Okamura T, Miyamoto Y

JAMA internal medicine 174 ( 4 ) 577 - 87 2014.04

ISSN 2168-6106

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Dentists' practice patterns regarding caries prevention: results from a dental practice-based research network.

Yokoyama Y, Kakudate N, Sumida F, Matsumoto Y, Gilbert GH, Gordan VV

BMJ open 3 ( 9 ) e003227 2013.09

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Men who have Sex with Men(MSM)におけるHIV感染予防行動を妨げる認知に関する検討

松高由佳, 古谷野淳子, 桑野真澄, 橋本充代, 本間隆之, 山崎浩司, 横山葉子, 日高庸晴

日本エイズ学会誌 ((一社)日本エイズ学会) 15 ( 2 ) 134 - 140 2013.05

ISSN 1344-9478

Men who have Sex with Men(MSM)向けHIV予防介入・教育に寄与するため、我が国のMSMのセイファーセックスを妨げるセルフトークのタイプについて検討した。方法は2009年に実施されたMSM対象のインターネットHIV予防介入プログラムにおいてUnprotected anal intercourese(UAI)を許容する認知(セルフトーク)のリスト30項目を提示し、回答を求めた。この236名分のデータを使用し結果、1)年齢層は20〜30代が約8割を占め、居住地は東京都54名(22.9%)、神奈川県27名(11.3%)、大阪府23名(9.7%)の順に多かった。2)因子分析は3つの因子構造であることが示唆された。第1因子は「安全神話」、第2因子は「あきらめ・開き直り」、第3因子は「セックスへの意味づけ」を表す因子と命名した。以上、このようにタイプが分類化されることは認知の傾向をより意識しやすくなり、予防介入場面で個人がセックスに求めている個別のニーズを把握でき、セイファーセックスを実現していく道を模索する上で研究の成果に活かすことができると考えられた。

A novel Internet-based blended learning programme providing core competency in clinical research.

Tsugihashi Y, Kakudate N, Yokoyama Y, Yamamoto Y, Mishina H, Fukumori N, Nakamura F, Takegami M, Ohno S, Wakita T, Watanabe K, Yamaguchi T, Fukuhara S

Journal of evaluation in clinical practice 19 ( 2 ) 250 - 5 2013.04

ISSN 1356-1294

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