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Keiko Iwai,1 Emi Ushigome,1 Isao Yokota,2 Saori Majima,1 Naoko Nakanishi,1 Yoshitaka Hashimoto,1 Hiroshi Okada,3 Takafumi Senmaru,1 Masahide Hamaguchi,1 Mai Asano,1 Masahiro Yamazaki,1 Michiaki Fukui1 1Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan; 2Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-0808, Japan; 3Department of Endocrinology and Diabetology, Matsushita Memorial Hospital, Moriguchi, Osaka, 570-8540, JapanCorrespondence: Emi UshigomeDepartment of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465, Kajii Cho, Kamigyo-ku, Kyoto-city, Kyoto 621-8585, JapanTel +81-75-251-5505Fax +81-75-252-3721Email emis@koto.kpu-m.ac.jpBackground: The coexistence of hypertension and diabetes mellitus significantly increases the risk of macrovascular complications in patients with diabetes. Home blood pressure is important because it is more strongly associated with target organ damage and total mortality than clinic blood pressure measurements. Regular moderate aerobic exercise has antihypertensive effects. This study aims to examine the effect of aerobic exercise therapy on blood pressure at home in patients with diabetes.Patients and Methods: In this crossover randomized controlled trial, 110 patients with type 2 diabetes will be randomly assigned to two groups: an exercise preceding group and an exercise lagging group. During the exercise period, patients will be instructed to walk either 30 minutes twice each day or 60 minutes once each day for at least 3 days per week. During the non-exercise period, patients will be permitted to perform physical activity associated with activities of daily life. Patients will be followed up for 56 days. The primary outcome will be the mean nocturnal blood pressure from day 24 to 28 during the exercise period compared to that during the non-exercise period. The secondary outcome will include variation in nocturnal blood pressure, mean blood pressure values and variation of morning and evening blood pressure from day 24 to 28 in the exercise period compared to the non-exercise period, body weight, body mass index and bioelectrical impedance analysis. Biochemical tests such as hemoglobin A1c level, blood glucose level, serum lipid profile, renal function, uric acid levels and liver function tests will also be measured.Discussion: This randomized controlled trial will provide critical information regarding the effectiveness of moderate exercise on nocturnal blood pressure reduction. If successful, the results of this randomized controlled trial may increase exercise motivation in people with diabetes and may lead to improvement or prevention of target organ damage and overall mortality.Trial Registration: Trial registration: University Hospital Medical Information Network, UMIN 000035973. Protocol version number: R000040969. Registration date: February 22, 2019. Recruitment began: June 19, 2019. The date of completion of recruitment: July 3, 2020. URL: http://www.umin.ac.jp.Keywords: nocturnal blood pressure, type 2 diabetes, aerobic exercise, randomized controlled trial

Iwai K, Ushigome E, Yokota I, et al. Diabetes Metab Syndr Obes. 2020;13:4747–4753. The authors have advised there was an error in the Institutional Review Board’s protocol version number. The correct protocol version number should read from R000040969 to ERB-C-1463-2. On page 4747, Abstract, Trial Registration section, the text “Protocol version number: R000040969. Registration date: February 22, 2019. Recruitment began: June 19, 2019” should read “Protocol version number: ERB-C-1463-2. Registration date: February 22, 2019. Recruitment began: June 19, 2019”. On page 4751, Ethics Approval and Informed Consent section, third sentence, the text “Protocol modifications will be approved by the medical research ethics committee of the Hospital of the Kyoto Prefectural University of Medicine (protocol reference number: R000040969)” should read “Protocol modifications will be approved by the medical research ethics committee of the Hospital of the Kyoto Prefectural University of Medicine (protocol reference number: ERB-C-1463-2)”. The authors wish to apologize for the error. Read the original article

Akiko Okamoto,1,2 Masaki Yamasaki,3 Isao Yokota,4 Maiko Mori,3 Megumi Matsuda,3 Yosuke Yamaguchi,3 Shunsuke Yamakita,3 Hiroshi Ueno,2 Teiji Sawa,3 Tetsuya Taguchi,1 Toyoshi Hosokawa,2 Fumimasa Amaya3 1Department of Endocrinological and Breast Surgery, 2Department of Pain Management and Palliative Care Medicine, 3Department of Anesthesiology, 4Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: Predictive value and accuracy of the acute pain trajectory were compared with those of pain intensity at 1 day after the surgery for pain prevalence at 6 months after the surgery.Materials and methods: Female patients scheduled for breast cancer surgery were eligible for this study. Patients were questioned about pain intensity daily during the 7 days after surgery. Presence of pain, its location, and intensity as well as the Japanese version of the quality of the recovery-40 (QOR-40) were determined in an interview prior to and at 6 months after the surgery. Acute pain trajectory was determined by a group-based trajectory modeling analysis that was based on the pain intensity at 1–7 days after surgery. Predictive value of the acute pain trajectory for the presence of pain at 6 months after the surgery was assessed by a logistic regression model. The predictive value was compared with pain intensity at 1 day after the surgery.Results: A total of 123 participants completed the 6-month follow-up. The three-cluster model (mild, moderate, and severe pain) was considered to be the most statistically appropriate model for the acute pain trajectory. After 6 months, 51.2% and 8.9% of participants reported pain and severe pain, respectively. Presence of pain at 6 months after the surgery was associated with poor recovery. The severe pain cluster was significantly associated with the presence of pain at 6 months after the surgery (adjusted odds ratio, 9.40; P

Anri Watanabe,1 Takashi Nakamae,1 Yuki Sakai,2 Seiji Nishida,1 Yoshinari Abe,1 Kei Yamada,3 Isao Yokota,4 Jin Narumoto1 1Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Neural Computation for Decision-Making, Advanced Telecommunications Research Institute International Brain Information Communication Research Laboratory Group, Kyoto, Japan; 3Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; 4Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: In recent years, a large number of studies have investigated obsessive–compulsive disorder (OCD) using diffusion-weighted images (DWIs) and have reported microstructural abnormalities in various regions, mainly the corpus callosum and cingulum. In the present study, we aimed to detect microstructural changes in the white matter using whole-brain tractography. Patients and methods: We obtained MRI data from 25 adult non-medicated OCD patients and 27 healthy controls. DWI data from MRI scans were analyzed by the automated probabilistic tractography method referred to as TRActs Constrained by UnderLying Anatomy (TRACULA). We investigated diffusivity parameters: fractional anisotropy, radial diffusivity (RD), axial diffusivity, and mean diffusivity in 18 major white matter tracts and examined indices to know which measurements in which fibers can predict the diagnosis of OCD. Results: Compared to healthy controls, OCD patients had significantly increased RD in the forceps major and a reduction of RD in the right cingulum angular (infracallosal) bundle. There was no correlation between these values and the clinical features. Conclusion: We found RD alterations in the forceps major and the right cingulum angular (infracallosal) bundle, which might be associated with myelination changes in the temporal and occipital regions in OCD. Our results suggest that the pathogenesis of OCD may include abonormality of myelination status in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions. Keywords: tractography, radial diffusivity, forceps major, cingulum

Atsumi Minamisawa,1 Jin Narumoto,1 Isao Yokota,2 Kenji Fukui1 1Department of Psychiatry, 2Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Background: Patient dropout from treatment can lead to a deterioration in clinical condition, thereby increasing the need for more intensive therapy that incurs substantial social and economic losses. The aim of this study was to identify factors related to psychiatric patient dropout at a university outpatient clinic in Japan.Methods: We retrospectively examined the medical charts of new psychiatric patients who were diagnosed with either a mood disorder (International Classification of Diseases, 10th revision, code: F3) or an anxiety disorder (F4) in the outpatient clinic at Kyoto Prefectural University of Medicine Hospital in Kyoto, Japan, between April 2010 and March 2013. The baseline characteristics of the patients (age, sex, Global Assessment of Functioning score, Clinical Global Impression–Severity of Illness score, education, occupation, marital status, duration of treatment, and prior treatment history), treating psychiatrist experience in years, and sex concordance between the patients and their treating psychiatrists were analyzed using Cox regression models.Results: From among 1,626 eligible new patients during the study period, 532 patients were enrolled in the study (F3: n=176; F4: n=356). The dropout rate was 35.7%, which was similar to that of previous studies. Higher educational level, being married, and lower Global Assessment of Functioning scores were associated with a lower dropout rate. Although psychiatrist experience was not significantly associated with patient dropout in the multivariate analysis, patients treated by less experienced psychiatrists had a higher hazard ratio for dropout (1.31; 95% confidence interval: 0.94–1.85).Conclusion: In order to reduce the dropout rate, special focus should be placed on patients with the factors identified in this study, and young psychiatrists should undergo further education to foster adherence. Keywords: patient dropout, psychiatry, outpatient care, mood disorders, anxiety disorders

Aim: To clarify the prevalence and degree of maternal microchimerism in Japanese children with type 1 diabetes, as well as its effect on phenotypic variation. Methods: We studied 153 Japanese children with type 1 diabetes, including 124 children positive for β‐cell autoantibodies, and their 71 unaffected siblings. The number of circulating microchimeric cells per 105 host cells was estimated by the use of quantitative‐polymerase chain reaction targeting non‐transmitted maternal human leukocyte antigen alleles. The results were compared to previous data from white European people. Phenotypic comparison was performed between maternal microchimerism carriers and non‐carriers with diabetes. Results: Maternal microchimerism was detected in 15% of children with autoantibody‐positive type 1 diabetes, 28% of children with autoantibody‐negative type 1 diabetes, and 16% of unaffected siblings. There were no differences in the prevalence or levels of maternal microchimerism among the three groups or between the children with type 1 diabetes and their unaffected siblings. Furthermore, maternal microchimerism carriers and non‐carriers exhibited similar phenotypes. Conclusions: Maternal microchimerism appears to be less common in Japanese children with type 1 diabetes than in white European people. Our data indicate that maternal microchimerism is unlikely to be a major trigger or a phenotypic determinant of type 1 diabetes in Japanese children and that the biological significance of maternal microchimerism in type 1 diabetes may differ among ethnic groups. What's new?: Maternal microchimerism appears to be less common in Japanese children with type 1 diabetes than in white European people with this condition.Circulating microchimeric cells are unlikely to be a major trigger or a phenotypic determinant of type 1 diabetes in Japanese children.The biological significance of maternal microchimerism in type 1 diabetes may differ among ethnic groups. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To evaluate comprehensively the use of the glycated albumin to HbA1c ratio for estimation of glycaemic control in the previous month. Methods: A total of 306 children with Type 1 diabetes mellitus underwent ≥10 simultaneous measurements of glycated albumin and HbA1c. Correlation and concordance rates were examined between HbA1c measurements taken 1 month apart (ΔHbA1c) and glycated albumin/HbA1c ratio fluctuations were calculated as Z‐scores from the cohort value at enrolment of this study cohort (method A) or the percent difference from the individual mean over time (method B). Results: Fluctuations in glycated albumin/HbA1c ratio (using both methods) were weakly but significantly correlated with ΔHbA1c, whereas concordance rates were significant for glycaemic deterioration but not for glycaemic improvement. Concordance rates were higher using method B than method A. Conclusions: The glycated albumin/HbA1c ratio was able to estimate glycaemic deterioration in the previous month, while estimation of glycaemic improvement in the preceding month was limited. Because method B provided a better estimate of recent glycaemic control than method A, the individual mean of several measurements of the glycated albumin/HbA1c ratio over time may also identify individuals with high or low haemoglobin glycation phenotypes in a given population, such as Japanese children with Type 1 diabetes, thereby allowing more effective diabetes management. [ABSTRACT FROM AUTHOR]

Aim To examine the contribution of PTPN2 coding variants to the risk of childhood-onset Type 1A diabetes. Methods PTPN2 mutation analysis was carried out for 169 unrelated Japanese people with childhood-onset Type 1A diabetes. We searched for coding variants that were absent or extremely rare in the general population and were scored as damaging by multiple in silico programs. We performed mRNA analysis and three-dimensional structural prediction of the detected variants, when possible. We also examined possible physical links between these variants and previously reported risk SNPs as well as clinical information from variant-positive children. Results One frameshift variant (p.Q286Yfs*24) and two probably damaging missense substitutions (p.C232W and p.R350Q) were identified in one child each. Of these, p.Q286Yfs*24 and p.C232W were hitherto unreported, while p.R350Q accounted for 2/121,122 alleles of the exome datasets. The p.Q286Yfs*24 variant did not encode stable mRNA, and p.C232W appeared to affect the structure of the tyrosine-protein phosphatase domain. The three variants were physically unrelated to known risk SNPs. The variant-positive children manifested Type 1A diabetes without additional clinical features and invariably carried risk human leukocyte antigen alleles. Conclusions The results provide the first indication that PTPN2 variants contribute to the risk of Type 1A diabetes, independently of known risk SNPs. PTPN2 coding variants possibly induce non-specific Type 1A diabetes phenotypes in individuals with human leukocyte antigen-mediated disease susceptibility. Our findings warrant further validation. [ABSTRACT FROM AUTHOR]

Aim To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children. Methods We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined. Results The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075]. Conclusions The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes. Methods We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis. Results Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10-5; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years. Conclusions The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood. [ABSTRACT FROM AUTHOR]