Nihon University School Research Articles

Clinical effect of equol supplementation in the treatment of desquamative gingivitis with 1-year follow-up.

Desquamative gingivitis (DG) is characterized by desquamative erosion, edematous erythema, and vesicle formation on the gingiva. Because of its prevalence in women during the pre- and postmenopausal period, its potential association with female hormones has been suggested. Equol is a soy isoflavone metabolite with a chemical structure similar to estrogen. Scientific evidence suggests that equol helps in alleviating menopausal symptoms. This study evaluated the clinical effect of a 12-month equol supplementation as a substitute for estrogen to alleviate DG symptoms. The study enrolled 16 women with DG who regularly visited Nihon University School of Dentistry Dental Hospital. Urinary equol levels, periodontal tissue examination, O'Leary's plaque control record, stimulated saliva flow rate, and gingival pain-related questionnaires were evaluated before and after the 12-month daily intake of 10 mg equol supplement. Equol supplementation led to a statistically significant improvement in bleeding on probing, visual findings, and reductions in the frequency and severity of gingival pain. Urinary equol testing and equol supplementation may be novel treatment options for female patients with DG.

Accreditation of Medical Education at Nihon University School of Medicine

Accreditation of Medical Education at Nihon University School of Medicine

Efficacy of apparent diffusion coefficient values for normal submandibular glands and acute submandibular sialadenitis

AbstractObjectiveThis study aimed to assess the apparent diffusion coefficient (ADC) values of normal salivary glands and acute submandibular sialadenitis (SS).MethodsThis retrospective study included 22 patients who underwent magnetic resonance imaging (MRI) at the Nihon University School of Dentistry between February 2018 and May 2022. ADC values were compared between the acute SS and control group. Data with non‐normality confirmed by Shapiro–Wilk test was analyzed using the Mann–Whitney U test, Spearman's correlation coefficient, and a receiver operating characteristic (ROC) curve. Statistical significance was set at p < 0.05.ResultsThe mean ADC values were 1.03 ± 0. 09 × 10−3 and 1.22 ± 0.17 × 10−3 mm2/s in the normal and acute SS groups, respectively (p < 0.001). ROC analysis revealed a cutoff ADC value of 1.1 for distinguishing acute SS from the normal.ConclusionThese findings suggest that ADC values are useful for the quantitative assessment of acute SS.

Neuroblastoma suppressor of tumorigenicity 1 is associated with the severity of interstitial fibrosis and kidney function decline in IgA nephropathy.

Recently, circulating neuroblastoma suppressor of tumorigenicity 1 (NBL1) was shown to be strongly associated with kidney disease progression and histological lesions in patients with diabetic kidney disease. This study aimed to examine whether serum NBL1 level was also associated with kidney function and renal histological findings in patients with IgA nephropathy. We evaluated the levels of NBL1 in 109 patients with newly diagnosed biopsy-proven primary IgAN, between 2009 and 2018, at the Nihon University School of Medicine Itabashi Hospital, Tokyo, Japan, using serum obtained immediately before therenal biopsy, and examined therelationship between serum NBL1, renal function and renal histological findings assessed using the Oxford Classification (MEST score). Furthermore, we analyzed the association of serum NBL1 with kidney function decline over timein patients with IgA nephropathy who had follow-up data on the estimated glomerular filtration rate (n = 76). Serum NBL1 levels in patients with newly diagnosed IgA nephropathy were elevated, as compared to those in healthy individuals (n = 93). Logistic regression analysis demonstrated that the serum NBL1 level was independently and significantly associated with tubular atrophy/interstitial fibrosis. Immunohistochemical staining revealed that NBL1 was highly expressed in the tubulointerstitium. Furthermore, Spearman's rank correlation identified a significant correlation between serum NBL1 level and estimated glomerular filtration rate slope. The serum NBL1 level was significantly associated with the severity of renal interstitial fibrosis and kidney disease progression in patients with newly diagnosedIgA nephropathy. Thus, circulating NBL1 may serve as a good biomarker for evaluating renal interstitial fibrosis and the risk of kidney disease progression.

One electrogram tracing tells all: What is the mechanism of this tachycardia and where is the catheter positioned?

Journal of Cardiovascular ElectrophysiologyEarly View EP ROUNDS One electrogram tracing tells all: What is the mechanism of this tachycardia and where is the catheter positioned? Taiga Honma, Taiga Honma Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanSearch for more papers by this authorShu Hirata MD, Shu Hirata MD orcid.org/0000-0003-1490-9488 Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanSearch for more papers by this authorKoichi Nagashima MD, PhD, Corresponding Author Koichi Nagashima MD, PhD [email protected] orcid.org/0000-0003-2326-225X Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan Correspondence Koichi Nagashima, MD, PhD, Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan. Email: [email protected]Search for more papers by this authorYasuo Okumura MD, PhD, Yasuo Okumura MD, PhD Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanSearch for more papers by this author Taiga Honma, Taiga Honma Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanSearch for more papers by this authorShu Hirata MD, Shu Hirata MD orcid.org/0000-0003-1490-9488 Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanSearch for more papers by this authorKoichi Nagashima MD, PhD, Corresponding Author Koichi Nagashima MD, PhD [email protected] orcid.org/0000-0003-2326-225X Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan Correspondence Koichi Nagashima, MD, PhD, Division of Cardiology, Department of Medicine, Nihon University School of Medicine, 30-1 Ohyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan. Email: [email protected]Search for more papers by this authorYasuo Okumura MD, PhD, Yasuo Okumura MD, PhD Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, JapanSearch for more papers by this author First published: 26 May 2023 https://doi.org/10.1111/jce.15957 Disclosures: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

The Factors Influencing Pregnant Women's Selection of Media Sources to Obtain Information on COVID-19 in Japan in 2021.

Pregnant women presumably gather information about the coronavirus disease 2019 (COVID-19) from various sources. However, it is difficult for pregnant women who are not medical professionals to source the appropriate information because of the infodemic related to the COVID-19 pandemic. Therefore, the objective of our study was to investigate how pregnant women gathered information about COVID-19 and COVID-19 vaccination. To address this issue, we conducted an online questionnaire survey between 5 October and 22 November 2021, which was approved by the Ethics Committee of Nihon University School of Medicine. We received 4962 responses after excluding 1179 insufficient answers. Our study found that age, occupation, and infection-risk anxiety influenced the selection of media for obtaining information. Pregnant women who were older, medical professionals, public servants, or educators tended to rely on specialized medical websites, whereas housewives tended to use mass media, social media, and sources with uncertain scientific evidence. Additionally, the number of weeks of gestation and the method of conception (natural or assisted reproductive conception) affected the selection of media. The accessibility of COVID-19 information for pregnant women was determined by their social background and pregnancy status. We need to continue making efforts to ensure that appropriate information is readily available to pregnant women and their families.

Survey of New Patients in the Department of Operative Dentistry at the Dental Hospital of Nihon University School of Dentistry at Matsudo

To determine the status of outpatients at the Dental Hospital of Nihon University School of Dentistry at Matsudo, we surveyed new patients examined in the Department of Operative Dentistry between April 1, 2019 and March 31, 2020. The following six items were extracted from the patients’ electronic dental records: referral（yes/no）, sex, age, residence, chief complaint, and site of chief complaint. Patients were subsequently divided into groups according to referral status for comparison of the other items. To identify factors associated with referrals, we performed logistic regression analysis with referral as the dependent variable and sex, address, age, chief complaint, and site as independent variables; odds ratios and 95% confidence intervals were calculated for each variable. Odds ratios were high for age, site, chief complaint, and sex and yielded the following conclusions concerning these variables. Regarding age, most patients in the referral group were in their 40s and 50s, while most patients in the non-referral group were in their 60s and 70s. The majority of new patients were female, while the percentage of male patients was slightly higher in the referral group than in the non-referral group. The most common sites were the molars in both groups. The most common chief complaints in the referral group and the non-referral group were apical periodontitis and class 2 caries, respectively. These results suggested that compared with the non-referral group, patients in the referral group were younger, were diagnosed earlier, and visited our hospital with greater expectation of dental preservation through high-quality treatment.

Vitamin D supplementation is effective for olanzapine-induced dyslipidemia.

Olanzapine is an atypical antipsychotic drug that is clinically applied in patients with schizophrenia. It increases the risk of dyslipidemia, a disturbance of lipid metabolic homeostasis, usually characterized by increased low-density lipoprotein (LDL) cholesterol and triglycerides, and accompanied by decreased high-density lipoprotein (HDL) in the serum. In this study, analyzing the FDA Adverse Event Reporting System, JMDC insurance claims, and electronic medical records from Nihon University School of Medicine revealed that a co-treated drug, vitamin D, can reduce the incidence of olanzapine-induced dyslipidemia. In the following experimental validations of this hypothesis, short-term oral olanzapine administration in mice caused a simultaneous increase and decrease in the levels of LDL and HDL cholesterol, respectively, while the triglyceride level remained unaffected. Cholecalciferol supplementation attenuated these deteriorations in blood lipid profiles. RNA-seq analysis was conducted on three cell types that are closely related to maintaining cholesterol metabolic balance (hepatocytes, adipocytes, and C2C12) to verify the direct effects of olanzapine and the functional metabolites of cholecalciferol (calcifediol and calcitriol). Consequently, the expression of cholesterol-biosynthesis-related genes was reduced in calcifediol- and calcitriol-treated C2C12 cells, which was likely to be mediated by activating the vitamin D receptor that subsequently inhibited the cholesterol biosynthesis process via insulin-induced gene 2 regulation. This clinical big-data-based drug repurposing approach is effective in finding a novel treatment with high clinical predictability and a well-defined molecular mechanism.

A nested case-control study of factors contributing to the development of medication-related osteonecrosis of the jaw in patients using bone resorption inhibitors in Mishima City.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by necrosis of the jawbone with intraoral bacterial infection and has a significant negative impact on oral health-related quality of life. Risk factors for the onset are unknown, and definitive therapeutic approaches have not yet been defined. A case-control study at a single institution in Mishima City was conducted. The purpose of this study was to examine in detail the factors that contribute to the development of MRONJ. Medical records of MRONJ patients who visited Mishima Dental Center, Nihon University School of Dentistry, during the period 2015-2021 were extracted. Counter-matched sampling design was used to select participants matched for sex, age, and smoking for this nested case-control study. The incidence factors were statistically examined by logistic regression analysis. Twelve MRONJ patients were used as cases and 32 controls were matched. After adjustment for potential confounders, injectable bisphosphonates (aOR = 24.5; 95% CI = 1.05, 575.0; P < 0.05) were significantly associated with the development of MRONJ. High-dose bisphosphonates may be a risk factor for the development of MRONJ. Patients who use these products require careful prophylactic dental treatment against inflammatory diseases, and dentists and physicians should maintain close communication.

Analysis of Four Measles Paintings Owned by the Nihon University School of Medicine archive:

Analysis of Four Measles Paintings Owned by the Nihon University School of Medicine archive:

Detection of Synergistic Interaction on an Additive Scale Between Two Drugs on Abnormal Elevation of Serum Alanine Aminotransferase Using Machine-Learning Algorithms.

Drug-induced liver injury (DILI) is a common adverse drug reaction, with abnormal elevation of serum alanine aminotransferase (ALT). Several clinical studies have investigated whether a combination of two drugs alters the reporting frequency of DILI using traditional statistical methods such as multiple logistic regression (MLR), but this model may over-fit the data. This study aimed to detect a synergistic interaction between two drugs on the risk of abnormal elevation of serum ALT in Japanese adult patients using three machine-learning algorithms: MLR, logistic least absolute shrinkage and selection operator (LASSO) regression, and extreme gradient boosting (XGBoost) algorithms. A total of 58,413 patients were extracted from Nihon University School of Medicine’s Clinical Data Warehouse and assigned to case (N = 4,152) and control (N = 54,261) groups. The MLR model over-fitted a training set. In the logistic LASSO regression model, three combinations showed relative excess risk due to interaction (RERI) for abnormal elevation of serum ALT: diclofenac and famotidine (RERI 2.427, 95% bootstrap confidence interval 1.226–11.003), acetaminophen and ambroxol (0.540, 0.087–4.625), and aspirin and cilostazol (0.188, 0.135–3.010). Moreover, diclofenac (adjusted odds ratio 1.319, 95% bootstrap confidence interval 1.189–2.821) and famotidine (1.643, 1.332–2.071) individually affected the risk of abnormal elevation of serum ALT. In the XGBoost model, not only the individual effects of diclofenac (feature importance 0.004) and famotidine (0.016), but also the interaction term (0.004) was included in important predictors. Although further study is needed, the combination of diclofenac and famotidine appears to increase the risk of abnormal elevation of serum ALT in the real world.

Current Status and Issues of Animal Experiments in Nihon University School of Medicine

Current Status and Issues of Animal Experiments in Nihon University School of Medicine

Identifying Antidepressants Less Likely to Cause Hyponatremia: Triangulation of Retrospective Cohort, Disproportionality, and Pharmacodynamic Studies.

Antidepressants are known to cause hyponatremia, but conflicting evidence exists regarding specific antidepressants. To identify antidepressants less likely to cause hyponatremia, we conducted a triangulation study integrating retrospective cohort, disproportionality, and pharmacodynamic studies. In the retrospective cohort study of patients (≥ 60 years) in Nihon University School of Medicine’s Clinical Data Warehouse (2004–2020), a significant decrease in serum sodium levels was observed within 30 days after initiation of a selective serotonin reuptake inhibitor (SSRI; mean change −1.00 ± 0.23 mmol/L, P < 0.001) or serotonin‐noradrenaline reuptake inhibitor (SNRI; −1.01 ± 0.31 mmol/L, P = 0.0013), whereas no decrease was found for a noradrenergic and specific serotonergic antidepressant (mirtazapine; +0.55 ± 0.47 mmol/L, P = 0.24). Within‐class comparison revealed no decrease in serum sodium levels for fluvoxamine (+0.74 ± 0.75 mmol/L, P = 0.33) among SSRIs and milnacipran (+0.08 ± 0.87 mmol/L, P = 0.93) among SNRIs. In the disproportionality analysis of patients (≥ 60 years) in the Japanese Adverse Drug Event Report database (2004–2020), a significant increase in hyponatremia reports was observed for SSRIs (reporting odds ratio 4.41, 95% confidence interval 3.58–5.45) and SNRIs (5.66, 4.38–7.31), but not for mirtazapine (1.08, 0.74–1.58), fluvoxamine (1.48, 0.94–2.32), and milnacipran (0.85, 0.45–1.62). Finally, pharmacoepidemiological–pharmacodynamic analysis revealed a significant correlation between the decrease in serum sodium levels and binding affinity for serotonin transporter (SERT; r = −0.84, P = 0.02), suggesting that lower binding affinity of mirtazapine, fluvoxamine, and milnacipran against SERT is responsible for the above difference. Although further research is needed, our data suggest that mirtazapine, fluvoxamine, and milnacipran are less likely to cause hyponatremia.

Minor Salivary Gland Tumors: A Retrospective Study of 37 Cases

Salivary gland tumors represent 2% - 6.5% of all head and neck tumors. Since salivary gland tumors have various clinical features and histological types, it is often difficult to diagnose and treat them. The aim of this study was to conduct a retrospective clinical-statistical analysis of 37 minor salivary gland tumors (MSGTs) treated in the Department of Oral Surgery at Nihon University School of Dentistry at Matsudo over a 16-year period. The frequencies and distributions of sex, age, occurrence site, preoperative examination (fine needle cytology and/or biopsy), treatment, and prognosis of the tumors were analyzed and compared with previous reports. The average age at diagnosis was 58.1 years (range 22 - 91 years). The peak occurrence of tumors was in the sixties (10 cases, 27.0%), followed by the forties (8 cases, 21.6%) and the seventies (7 cases, 18.9%). The average age of patients with benign tumors was 56.8 years (range 22 - 91 years). For malignant tumors, the average age was 61.7 years (range 42 - 81 years). The male-female ratio was 1:2.1 for all minor salivary gland tumors, 1:2.4 for benign tumors, and 1.5:1 for malignant tumors. There were 27 (73.0%) benign and 10 (27.0%) malignant tumors. Pleomorphic adenoma (PA) was the most common tumor (24 (64.9%) cases). Most salivary gland tumors originated from the palate (21 cases, 56.8%); the second most common site was the buccal mucosa (14 cases, 37.8%). For most patients, an intraoral mass was the primary presentation, and the second most common symptom was swelling. Surgical treatment was performed for all cases, both benign and malignant tumors. There was one case of local recurrence of PA, as well as one of multiple lung metastases after surgery for adenoid cystic carcinoma. Diagnosis and treatment of MSGTs are often delayed because the patients have few symptoms, and it is difficult to distinguish benign from malignant tumors. More cases need to be examined in the future, and the diagnostic accuracy of imaging and histopathological diagnosis needs to be improved.

Relationship between apparent diffusion coefficient value of the bone marrow and cortical width of the mandible in the healthy patients

ObjectivesDiffusion-weighted imaging (DWI) is a technique reflecting motion of water proton within the tissue. Studies have investigated the apparent diffusion coefficient (ADC) of bone marrow in musculoskeletal lesions. This study assessed the correlation between the ADC of bone marrow in the mandible and the mandibular cortical width (MCW) in the healthy patients. MethodsThis research was a retrospective cohort study. The patient underwent echo planar (EPI)-DWI and panoramic X-ray at the Nihon University School of Dentistry between April 2020 and October 2020. The predictor variable was mean MCW. The primary outcome variable was the mean ADC of mandibular bone marrow. The other variable was age. Data were analyzed using a Mann-Whitney U test, Spearman’s correlation coefficient. Statistical significance was set at p < 0.05. ResultsWe analyzed the records of 18 men (mean age, 44.94, age range 20–73 years) and 40 women (mean age, 47.98, age range 21–78 years). There was not significant difference between sex and mean ADC value, mean MCW (p = 0.853 and p= 0.43, respectively). There was a significant positive correlation between MCW and the ADC of the mandibular bone marrow (r = .493, p < 0.001). ConclusionsThis suggests that in addition to evaluating the MCW, which is currently used for bone quality evaluation, measuring the ADC of bone marrow in the mandible could contribute toward the examination of bone quality and diseases.

Efficacy of diffusion-weighted magnetic resonance imaging in the diagnosis of osteomyelitis of the mandible

This retrospective cohort study aimed to determine the diagnostic utility of apparent diffusion coefficient (ADC) values in the quantitative evaluation of mandibular osteomyelitis. We analyzed the records of 70 patients aged 30 to 90 years, with and without osteomyelitis, who underwent magnetic resonance imaging at the Nihon University School of Dentistry between April 2017 and March 2019. The mean ADC of bone marrow of patients without osteomyelitis and those with acute and chronic osteomyelitis of the mandible were calculated. Differences in ADC overall and in pair-wise comparisons were analyzed. Correlations with patient age were also calculated. The mean ADC values in the nonosteomyelitis, acute osteomyelitis, and chronic osteomyelitis groups were 0.87 ± 0.15×10-3, 1.24 ± 0.11×10-3, and 1.07 ± 0.13×10-3 mm2/s, respectively (P < .001 for all pair-wise comparisons). Receiver operating characteristic curve analysis revealed an ADC cut-off of 0.98 for osteomyelitis. Diagnostic values for predicting osteomyelitis were ≥ .81. No correlations of osteomyelitis with age were found. The ADC was significantly higher in the osteomyelitis groups than in the nonosteomyelitis group. This suggests that ADC may be a useful parameter for quantitative evaluation of mandibular osteomyelitis.

Effects of Fibrates on Risk of Development of Diabetic Retinopathy in Japanese Working Age Patients with Type 2 Diabetes and Dyslipidemia: a Retrospective Cohort Study

The aims of the present study were to investigate the effects of fenofibrate and bezafibrate on the risk of development of diabetic retinopathy (DR) in patients with type 2 diabetes and dyslipidemia. Japanese working age patients with type 2 diabetes and dyslipidemia were extracted from the Nihon University School of Medicine Clinical Data Warehouse. These patients were divided into three groups: control group (n=2549), fenofibrate group (n=40), and bezafibrate group (n=135). Multivariate logistic regression analysis was performed to assess the association between fibrates and the development of DR. After adjustment for covariates, fenofibrate showed no association with the risk of DR [adjusted odds ratio (OR), 0.160; 95% CI, 0.021-1.209; p=0.0758]. Bezafibrate also showed no association with the risk of DR (adjusted OR, 0.731; 95% CI, 0.411-1.299; p=0.2855). However, poor control of hemoglobin A1c (HbA1c ≥8.0%; adjusted OR, 3.623; 95% CI, 2.649-4.956; p<0.0001) and high low-density lipoprotein cholesterol (LDL-C ≥140 mg/dL; adjusted OR, 1.399; 95% CI, 1.013-1.932; p=0.0415) within the follow-up period of type 2 diabetes and dyslipidemia increased the risk of DR. Our results suggested that to prevent development of DR in patients with type 2 diabetes and dyslipidemia, controlling LDL-C levels as well as HbA1c levels under coexistence type 2 diabetes and dyslipidemia is more important than the selection of fibrate.

4. Clinical Pharmacological Research Using Medical Big Data from 22 Million Patients over 15 Years in Nihon University School of Medicine

4. Clinical Pharmacological Research Using Medical Big Data from 22 Million Patients over 15 Years in Nihon University School of Medicine

One electrogram-tracing tells all: What is the mechanism of this supraventricular tachycardia?

A 72-year-old man without overt structural heart disease was referred to our institution for catheter ablation of a narrow QRS tachycardia. This article is protected by copyright. All rights reserved.

Trends in Sleep Problems Among Japanese Adolescents: 2004 to 2017

Background: Adolescence is a period of physical, mental, and social development. Sleep problems in adolescence, such as insomnia and short sleep duration, have been associated with physical and mental health problems. Little is known about the recent trends in sleep problems among adolescents. This study aimed to examine trends in sleep problems among Japanese adolescents. Methods: Using data from the Lifestyle Survey of Adolescents collected in 2004, 2008, 2010, 2012, 2014, and 2017, we calculated the prevalence of insomnia, short sleep duration, late bedtime, long sleep duration, and poor sleep quality. Multivariable logistic regression analysis models were used to examine the association of each sleep problem and survey years. Sampling weights were constructed based on participation rates. Findings: We analyzed data from 545,285 Japanese adolescents. Results indicated that, since 2004, the odds of insomnia decreased (AOR 0·86, 95%CI 0·84-0 ·88), as did the odds of short sleep duration (AOR 0·89, 95%CI 0·90-0·94) and poor sleep quality (AOR 0·93, 95%CI 0·92-0·95). However, the odds of late bedtime tended to increase (AOR 1·07, 95%CI 1·05-1·10) during this period. Interpretation: The prevalence of insomnia symptoms, short sleep duration, and poor sleep quality among adolescents decreased from 2004 to 2017. However, the prevalence of late bedtime increased. These changes are both relieving and concerning. Teachers, parents, and health professionals should consider educating adolescents regarding sleep hygiene, adjusting schedules of extracurricular activities, and enhancing time management to improve their sleep quality. Funding Statement: This study was supported by a grant for Comprehensive Research on Lifestyle-Related Diseases including Cardiovascular Diseases and Diabetes Mellitus by the Ministry of Health and Welfare Health Science Research Fund in Japan (grant no. 29060801). Declaration of Interests: Adam P. Spira received an honorarium from Springer Nature Switzerland AG for Guest Editing a Special Issue of Current Sleep Medicine Reports. The other authors declare no conflicts of interest associated with this manuscript. Ethics Approval Statement: Informed written consent was obtained from all study participants. Due to the new epidemiological research guidelines, informed consent was obtained from each junior high school student’s parent or guardian in the 2017 survey. Parents’ and guardians’ informed consent was not required by the guidelines governing anonymous and non-invasive research entailing students who had finished junior high school in the earlier years. The teachers explained the nature of confidentiality and voluntary participation to all the students, and completed questionnaires were returned to the working group in sealed envelopes. This protocol is in accordance with the Japanese Ethical Guidelines for Epidemiological Research announced by the Ministry of Health, Labour and Welfare and the Ministry of Education, Culture, Sports, Science and Technology of Japan. The working group used anonymized questionnaires to prevent the identification of individual participants and to safeguard their privacy. This study was approved by the ethical review board of the Nihon University School of Medicine.