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Purpose Weight bias internalization (WBI) is significantly associated with negative physiological and psychological consequences. Given its negative effects, appropriate measurement of WBI is required for weight management and mental and physical health in people with weight problems. One of the most reliable and frequently used questionnaires to assess WBI is the Weight Self-Stigma Questionnaire (WSSQ). However, a Japanese version of the WSSQ has not yet been developed. Thus, the current study aimed to develop a Japanese version of the WSSQ (WSSQ-J) and validate its psychometric properties in the Japanese context. Methods A total of 1454 Japanese participants (age 34.44 ± 6.92; male = 498) with diverse weight statuses (Body mass index: 21.44 ± 3.52, 13.79–41.40 kg/m2) completed an online survey for the WSSQ-J. The internal consistency of the WSSQ-J was estimated by calculating Cronbach’s α. Confirmatory factor analysis (CFA) was then carried out to confirm that the factor structure of the WSSQ-J was the same as that of the subscales of the original WSSQ. Results The WSSQ-J had a Cronbach’s α of 0.917, indicating good internal consistency. In CFA, the comparative fit index was 0.945, the root mean square error of approximation was 0.085, and the standardized root mean square residual was 0.040, indicating that the two-factor model showed satisfactory goodness-of-fit. Conclusion This study replicated the original findings related to the WSSQ, showing that the WSSQ-J is a reliable WBI questionnaire consisting of two factors. Therefore, the WSSQ-J would be a reliable tool for assessing WBI among Japanese. Level of evidence Level V, descriptive cross-sectional study.

Aim To evaluate the safety and pharmacokinetics of cotadutide, a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, in overweight Asian participants with or without type 2 diabetes (T2D). Materials and methods In the phase 1, randomized, blinded, single-ascending dose study, 24 Japanese and eight Chinese healthy adults (body mass index [BMI] 23-40 kg/m2 ) received one subcutaneous dose of cotadutide (50-150 or 100 μg, respectively) or placebo. The primary endpoint was safety. In the phase 2a, randomized, double-blinded, parallel dose-ranging study with forced uptitration, 61 Japanese adults with T2D (BMI 24-40 kg/m2 ; HbA1c 7.0%-10.5%) received cotadutide (100, 200, 300 μg) or placebo for 48 days. Co-primary endpoints were safety/tolerability, change in glucose AUC0-4h and body weight. Results Significant reductions from baseline to day 48 were observed with cotadutide for glucose AUC0-4h (33.6%-42.1% reduction vs. +2.5% with placebo; 95% CIs: 100 μg -45.7%, -33.7%; 200 μg -35.6%, -23.7%; 300 μg -45.0%, -30.8%; placebo 3.4%, 8.3%) and body weight (1.3%-2.5% decrease vs. +0.8% with placebo; 95% CIs: 100 μg -3.4%, -0.8%; 200 μg -4.7%, -2.0%; 300 μg -4.6%, -2.1%; placebo -2.1%, 0.4%). The most common adverse events with cotadutide were mild gastrointestinal symptoms with no serious adverse events. Increased pulse rate with cotadutide versus placebo is consistent with GLP-1 monoagonists. Conclusions Once-daily cotadutide was effective and well tolerated up to 300 μg in overweight Japanese patients with T2D. Further evaluation in Asian populations is warranted.

Childhood socioeconomic status is robustly associated with various children’s cognitive factors and neural mechanisms. Here we show the association of childhood socioeconomic status with psychometric intelligence and mean diffusivity and fractional anisotropy using diffusion tensor imaging at the baseline experiment (N = 285) and longitudinal changes in these metrics after 3.0 ± 0.3 years (N = 223) in a large sample of normal Japanese children (mean age = 11.2 ± 3.1 years). After correcting for confounding factors, cross-sectional and longitudinal analyses show that higher childhood socioeconomic status is associated with greater baseline and baseline to follow-up increase of psychometric intelligence and mean diffusivity in areas around the bilateral fusiform gyrus. These results demonstrate that higher socioeconomic status is associated with higher psychometric intelligence measures and altered microstructural properties in the fusiform gyrus which plays a key role in reading and letter recognition and further augmentation of such tendencies during development. Definitive conclusions regarding the causality of these relationships requires intervention and physiological studies. However, the current findings should be considered when developing and revising policies regarding education., Takeuchi et al perform cross-sectional and longitudinal analyses of associations between childhood socioeconomic status and psychometric intelligence as well as microstructural brain development in Japanese children. They report that higher socioeconomic status is associated with greater psychometric intelligence and altered microstructural properties in the fusiform gyrus which plays a role in reading and letter recognition.

Aim To examine the long‐term efficacy and safety of dapagliflozin, a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor used to treat type 1 diabetes, in the Japanese subpopulation of the DEPICT‐2 study. Materials and Methods Patients with type 1 diabetes were randomized to dapagliflozin 5 mg (n = 55), dapagliflozin 10 mg (n = 41) or placebo (n = 58) plus insulin for a 24‐week, double‐blind period followed by a 28‐week, single‐blind extension phase. Results From baseline to 24 weeks, dapagliflozin reduced HbA1c compared with placebo (mean change of −0.58% and −0.80% for 5 and 10 mg, respectively), and an HbA1c reduction was observed up to 52 weeks. Compared with placebo, dapagliflozin 5 and 10 mg increased the proportion of patients achieving HbA1c reductions of 0.5% or more without severe hypoglycaemia events and reduced glycaemic variability assessed via continuous glucose monitoring. Both dapagliflozin doses decreased body weight and total daily insulin dose at 24 weeks compared with placebo; these reductions were maintained up to 52 weeks. Diabetic ketoacidosis occurred in both dapagliflozin groups (one and two cases, respectively) but not with placebo. Conclusions Efficacy and safety results from the Japanese subpopulation of the DEPICT‐2 study were generally consistent with those from the overall population, indicating that long‐term dapagliflozin adjunct to insulin therapy improves glycaemic control without an increased risk of hypoglycaemia but with a risk of diabetic ketoacidosis in Japanese patients with type 1 diabetes.

Synesthesia is a condition in which the perception of a stimulus in one modality automatically triggers a secondary sensation in another modality or processing stream. Our study focused on grapheme-color synesthesia, in which the visual perception of letters or numbers (graphemes) induces a specific color sensation (the synesthetic color). Grapheme-color synesthetes do not typically experience colors for novel graphemes. However, synesthetic colors associated with familiar graphemes can be transferred to graphemes learned later, even in adulthood. A previous study has shown that such a transfer can take place after only a 10-min writing exercise. In this study, we found that this immediate transfer occurs only when the synesthetic colors for familiar graphemes contribute to the discrimination of the graphemes to be learned. Synesthetes learned six novel graphemes, each of which was arbitrarily associated with one of six familiar graphemes. Half of the synesthetes were assigned to the heterogeneous condition, in which the synesthetic colors of one group of familiar graphemes were different from one another. The other half of the synesthetes were assigned to the homogeneous condition, in which the various colors of a whole group of familiar graphemes were categorically the same. After this learning session, less transfer of synesthetic colors to novel graphemes from the corresponding familiar graphemes occurred in the homogeneous condition than in the heterogeneous condition. These results support the view that synesthetic colors for graphemes may function as a grapheme acquisition aid.

Childhood is an extremely important time for neural development that has a critical role in human intelligence. Efficient information processing is crucial for higher intelligence, so the intra- or inter-hemispheric interaction is vital. However, the relationship between neuroanatomical connections and intelligence in typically developing children, as well as sex differences in this relationship, remains unknown.Participants were 253 typically developing children (121 boys and 132 girls) aged 5-18. We acquired diffusion tensor imaging data and intelligence using an age-appropriate version of the IQ test; Wechsler Intelligence Scale for Children (WISC) or Wechsler Adult Intelligence Scale (WAIS). We conducted whole-brain multiple regression analysis to investigate the association between fractional anisotropy (FA), which reflects white matter microstructural properties, and each composite score of IQ test (full-scale IQ, performance IQ, and verbal IQ).FA was positively correlated with full-scale IQ in bilateral inferior occipitofrontal fasciculus, genu, and splenium of corpus callosum (CC). FA in the right superior longitudinal fasciculus, bilateral inferior longitudinal fasciculus, and splenium of CC were also positively correlated with performance IQ. Furthermore, we found significant sex interaction between FA in the CC and verbal IQ. FA was positively correlated in boys, and negatively correlated in girls.Results suggest that efficient anatomical connectivity between parietal and frontal regions is crucial for children's intelligence. Moreover, inter-hemispheric connections play a critical role in verbal abilities in boys.

Aims To investigate the safety and tolerability of 5 and 10 mg dapagliflozin added to insulin therapy over 52 weeks in Japanese patients with inadequately controlled type 1 diabetes mellitus (T1DM). Materials and methods This randomized, open‐label, parallel‐group, multicentre phase III clinical trial was conducted from October 26, 2015 to June 15, 2017. The primary endpoint was the occurrence of adverse events such as hypoglycaemia and diabetic ketoacidosis. Secondary endpoints included changes in glycaemic parameters, total daily insulin dosage and body weight over time. The efficacy of dapagliflozin in patients stratified by body mass index (BMI)

Grapheme-color synesthetes experience graphemes as having a consistent color (e.g., “N is turquoise”). Synesthetes’ specific associations (which letter is which color) are influenced by linguistic properties (letter frequency, phonetic similarity, etc.), and plausibly reveal the characteristics of underlying letter representations. Despite their clear linguistic origin, these influences (termed “Regulatory Factors”, RFs) are almost always studied in a single language, typically English. Here, we measure the influence of three RFs (previously examined only in English) in Dutch, English, Greek, Japanese, Korean, Russian, and Spanish synesthetes. For two RFs, effect size significantly differed between languages. In contrast, an RF which we predicted to be universal (because it is shaped by prelinguistic shape-color associations) did not differ between languages. Our results suggest that monolingual synesthesia studies should be interpreted with caution. Furthermore, they show how synesthetic associations offer an exceptional opportunity to study linguistic and prelinguistic influences on letter representations in different languages.

Background: Immunogenicity and safety of the AZD1222 (ChAdOx1 nCoV-19) vaccine was evaluated in Japanese adults in an ongoing phase 1/2, randomized, double-blind, parallel-group, placebo-controlled, multi-centre trial (NCT04568031). Methods: Adults (n=256, age ≥18 years) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age into 18–55- (n=128), 56–69- (n=86) and ≥70-year-old cohorts (n=42), and randomized 3:1 to receive AZD1222 or placebo (two intramuscular injections 4 weeks apart). Immunogenicity and safety were coprimary endpoints. Data collected up to Day 57 are reported. Results: Positive seroresponses to SARS-CoV-2 spike and receptor-binding domain antigens were seen in all 174 participants who received two doses of AZD1222. Neutralizing antibody seroresponses were seen in 67.5%, 60.3% and 50.0% of participants receiving AZD1222 aged 18–55, 56–69 and ≥70 years, respectively. Solicited adverse events (AEs) were typically mild/moderate in severity and included pain and tenderness at the injection site, malaise, fatigue, muscle pain and headache. Common unsolicited AEs included pain and tenderness at the injection site, fatigue and elevated body temperature. No vaccine-related serious AEs or deaths were reported. Conclusions: AZD1222 elicited a strong humoral immune response against SARS-CoV-2, and was well tolerated in Japanese participants, including elderly participants.

Aims To assess the pharmacokinetics/pharmacodynamics (PK/PD) of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor that increases urinary glucose excretion (UGE) and its major metabolite, dapagliflozin-3-O-glucuronide (D3OG), in Japanese patients with type 1 diabetes (T1D) and inadequate glycaemic control (HbA1c 7%-10%). Materials and methods Japanese patients (18-65 years) with inadequately controlled T1D were randomized 1:1:1 to dapagliflozin 5 mg, 10 mg or placebo (n = 14 each) once daily for 7 days, with adjustable insulin. The PK/PD characteristics of dapagliflozin and D3OG were assessed on Day 7. Patients underwent follow-up evaluation on Days 8 and 14. Adverse events (AEs), hypoglycaemic episodes and events of diabetic ketoacidosis (DKA) were recorded over the treatment and follow-up periods. Results A total of 42 randomized patients received dapagliflozin or placebo. PK variables increased in a dose-dependent manner. D3OG was generated rapidly, with a median time to maximum plasma concentration of 2.0 hours (1.0-3.0). The dapagliflozin dose-UGE relationship was attenuated, with larger insulin dose reductions than anticipated. Mean percent (standard error) changes in total daily insulin dose from baseline to Day 7 were - 36.86% (3.32), -39.13% (2.68) and - 4.97% (5.28) for dapagliflozin 5 mg and 10 mg and for placebo, respectively. No DKA was reported. AEs were consistent with the established dapagliflozin safety profile. There was no increase in hypoglycaemia. Conclusions The PK and safety profiles of dapagliflozin in Japanese patients with T1D were consistent with previous studies, but with an unanticipated attenuation of the PD dose-response measured as UGE.

To evaluate the safety and pharmacokinetics of cotadutide, a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, in overweight Asian participants with or without type 2 diabetes (T2D).In the phase 1, randomized, blinded, single-ascending dose study, 24 Japanese and eight Chinese healthy adults (body mass index [BMI] 23-40 kg/mSignificant reductions from baseline to day 48 were observed with cotadutide for glucose AUCOnce-daily cotadutide was effective and well tolerated up to 300 μg in overweight Japanese patients with T2D. Further evaluation in Asian populations is warranted.

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (FY2018 ∼ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. The Harmonization protocol (HARP) was established for five high-quality 3T scanners to obtain multimodal brain images including T1 and T2-weighted, resting state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, providing high reproducibility and sensitivity to subject-specific connectome. A total of 75 TS, as well as patients with various psychiatric and neurological disorders, are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a rigorous, prospective harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

This research investigated how children build up the language-specific system of the color lexicon, examining factors that play important roles for the construction of an adult-like color lexicon. We had 3-, 4-, and 5-year-old Japanese-speaking children and adults (n = 20, 18, 19, and 19, respectively) produce names for 93 color swatches. The results showed that children of all ages were able to apply most of the chromatic words to the colors close to the center of each category, but even 5-year-olds struggle to delineate the boundaries between the words. Furthermore, the model analyses revealed that broad-covering and high-frequency words are mapped to the center of the lexical category earlier. However, cross-individual consistency in adults' use contributed most strongly for the adult-like boundary delineation. The results suggest that the process of system construction consists of at least two steps (i.e., mapping words to their category center and finding appropriate boundaries between neighboring words), with the quantity and the quality of the input contributing differently to the steps.

Irony comprehension requires integration of social contextual information. Previous studies have investigated temporal aspects of irony processing and its neural substrates using psychological/electroencephalogram or functional magnetic resonance imaging methods, but have not clarified the temporospatial neural mechanisms of irony comprehension. Therefore, we used magnetoencephalography to investigate the neural generators of alpha-band (8-13Hz) event-related desynchronization (ERD) occurring from 600 to 900ms following the onset of a critical sentence at which social situational contexts activated ironic representation. We found that the right anterior temporal lobe, which is involved in processing social knowledge and evaluating others' intentions, exhibited stronger alpha ERD following an ironic statement than following a literal statement. We also found that alpha power in the left anterior temporal lobe correlated with the participants' communication abilities. These results elucidate the temporospatial neural mechanisms of language comprehension in social contexts, including non-literal processing.

A 65-year-old woman visited our hospital due to right chest pain and dyspnea on exertion. Chest radiography revealed decreased permeability of the right lung. Computed tomography demonstrated a huge mass in the right upper lobe and right pleural effusion. Right pleural effusion cytology yielded a diagnosis of adenocarcinoma and was positive for mutation of epidermal growth factor receptor (EGFR; exon 21 L858R). Afatinib was selected for the initial treatment. Multiple tumors regressed remarkably, but then rapidly progressed 3 months later. We performed re-biopsy to detect the mechanism of resistance to afatinib. Histopathology revealed a mixture of small cell carcinoma (SCC) and adenocarcinoma harboring same EGFR mutation. To the best of our knowledge, this is the first report of transformation to SCC after treatment with afatinib.

A 73-year-old man was referred to our hospital after a 2-week history of bloody sputum and cough. Computed tomography (CT) images of the chest showed a mass grouped with mediastinal lymph nodes, and bronchoscopy showed a projecting mass in the right main bronchus. After a transbronchial biopsy, the patient was diagnosed with squamous cell carcinoma (T4N2M0 stage IIIB). The patient was treated with systemic chemotherapy, consisting of cisplatin (40 mg/m2, days 1 and 8) and docetaxel (30 mg/m2, days 1 and 8), and concurrent thoracic irradiation at a daily dose of 2 Gy. On day 35 of treatment, the patient complained of a sore throat and cough. A CT of the chest showed punctate low-attenuation foci between the esophagus and bronchus. Gastrointestinal endoscopy and bronchoscopy demonstrated a fistula in the middle intrathoracic esophagus and the left main bronchus. The patient’s symptoms gradually improved, and the fistula was closed after the suspension of chemoradiotherapy. Radiotherapy was resumed and completed on day 82. However, on day 108, he developed a fever and cough, and a tumor with fistula was revealed in the right main bronchus. He had an esophageal stent inserted, but he later died of sudden hemoptysis.

Aims To evaluate the efficacy and safety of dapagliflozin as add-on to insulin in Japanese patients with type 2 diabetes. Materials and methods Insulin-treated Japanese patients were randomized to 5 mg dapagliflozin or placebo during a 16-week double-blind treatment period. Both groups then received dapagliflozin 5 or 10 mg (the dose was increased at or after week 24 if glycated haemoglobin [HbA1c] at the previous visit was >7.5%) during a 36-week open-label extension period. The exploratory efficacy endpoint was to assess the maintenance efficacy of 5/10 mg dapagliflozin + insulin over 52 weeks of treatment. Safety was assessed in terms of adverse events, laboratory variables and vital signs. Results The changes in HbA1c from baseline to weeks 16 and 52 were −0.62% and −0.74%, respectively, in the dapagliflozin group, vs −0.08% and −0.83%, respectively, in the placebo–dapagliflozin group. Body weight decreased at both time points in the dapagliflozin group and after switching to open-label dapagliflozin in the placebo–dapagliflozin group. The total insulin dose decreased slightly after starting dapagliflozin. Adverse events occurred in 82.9% and 71.7% of patients in the dapagliflozin and placebo–dapagliflozin groups, respectively. Hypoglycaemia occurred in 35.0% and 41.7% of patients in the dapagliflozin and placebo–dapagliflozin groups, respectively, but the incidence was not increased by use of dapagliflozin in either trial period. Genital/urinary tract infections, renal impairment/failure, volume depletion, fracture and hepatic disorders occurred in ≤5% of patients. Conclusion This trial showed that administration of dapagliflozin as an add-on to insulin therapy was effective, was well tolerated and had insulin-sparing effects in Japanese patients with type 2 diabetes.

Sound symbolism, which is the systematic and non-arbitrary link between a word and its meaning, has been suggested to bootstrap language acquisition in infants. However, it is unclear how sound symbolism is processed in the infants’ brain. To address this issue, we investigated the cortical response in 11-month-old infants in relation to sound-symbolic correspondences using near-infrared spectroscopy (NIRS). Two types of stimuli were presented: a novel visual stimulus (e.g., a round shape) followed by a novel auditory stimulus that either sound-symbolically matched (moma) or mismatched (kipi) the shape. We found a significant hemodynamic increase in the right temporal area, when the sound and the referent sound were symbolically matched, but this effect was limited to the moma stimulus. The anatomical locus corresponds to the right posterior superior temporal sulcus (rSTS), which is thought to process sound symbolism in adults. These findings suggest that prelinguistic infants have the biological basis to detect cross-modal correspondences between word sounds and visual referents.

This research investigated how children build up the language-specific system of the color lexicon, examining factors that play important roles for the construction of an adult-like color lexicon. We had 3-, 4-, and 5-year-old Japanese-speaking children and adults (n = 20, 18, 19, and 19, respectively) produce names for 93 color swatches. The results showed that children of all ages were able to apply most of the chromatic words to the colors close to the center of each category, but even 5-year-olds struggle to delineate the boundaries between the words. Furthermore, the model analyses revealed that broad-covering and high-frequency words are mapped to the center of the lexical category earlier. However, cross-individual consistency in adults' use contributed most strongly for the adult-like boundary delineation. The results suggest that the process of system construction consists of at least two steps (i.e., mapping words to their category center and finding appropriate boundaries between neighboring words), with the quantity and the quality of the input contributing differently to the steps.

Grapheme-color synesthesia is a condition in which the visual perception of letters or numbers induces a specific color sensation. The consistency of grapheme-color association has been considered as a fundamental characteristic of synesthesia. However, recent studies have indicated that this association can change across the adult lifespan, and it has become necessary to investigate the factors behind the changes within each synesthete. We conducted a longitudinal study of Japanese adult synesthetes to investigate long-term (5–8 years) changes in color responses to 300 graphemes (alphanumeric and Japanese characters). Graphemes with lower long-term consistency of synesthetic association also tended to have lower short-term consistency, indicating that grapheme-color association's consistency is determined for each grapheme. Further, less familiar graphemes had less consistent associations with their synesthetic colors. These findings suggest that a stronger grapheme-color association is formed for more familiar graphemes, leading to the consolidation of synesthetic color for such graphemes.

Highlights • The Brain/MINDS beyond project plans to collect multi-site/scanner brain MRI data. • Prospective harmonization of MRI was achieved by standardizing scanning protocols. • The preliminary data showed moderate reliability of brain connectome data. • Completing traveling subject plan will allow robust statistical harmonization. • Scanning protocols are publicly available and data will also be shared by 2024., Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. A high-quality scanning protocol, Harmonization Protocol (HARP), was established for five high-quality 3 T scanners to obtain multimodal brain images including T1 and T2-weighted, resting-state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, suggesting sensitivity to subject-specific connectome. A total of 75 TS and more than two thousand patients with various psychiatric and neurological disorders are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a prospective, multi-level harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

Psychological studies showed the quantity of reading habit affects the development of their reading skills, various language skills, and knowledge. However, despite a vast amount of literature, the effects of reading habit on the development of white matter (WM) structures critical to language and reading processes have never been investigated. In this study, we used the fractional anisotropy (FA) measure of diffusion tensor imaging to measure WM microstructural properties and examined cross-sectional and longitudinal correlations between reading habit and FA of the WM bundles in a large sample of normal children. In both cross-sectional and longitudinal analyses, we found that greater strength of reading habit positively affected FA in the left arcuate fasciculus (AF), in the left inferior fronto-occipital fasciculus (IFOF), and in the left posterior corona radiata (PCR). Consistent with previous studies, we also confirmed the significance or a tendency for positive correlation between the strength of reading habit and the Verbal Comprehension score in cross-sectional and longitudinal analyses. These cross-sectional and longitudinal findings indicate that a healthy reading habit may be directly or indirectly associated with the advanced development of WM critical to reading and language processes. Future intervention studies are needed to determine the causal effects of reading habits on WM in normal children.

Introduction Dapagliflozin treatment when added to insulin therapy in Japanese patients with type 2 diabetes remains to be evaluated. Materials and Methods This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled study to evaluate efficacy (at 16 weeks) and long-term safety (at 52 weeks) of dapagliflozin in addition to insulin therapy. The interim analysis was carried out at week 16 to assess the efficacy and safety profiles. The patients receiving insulin (n = 182) were randomized to either dapagliflozin 5 mg or a placebo at a 2:1 ratio. The primary efficacy end-point was the change in hemoglobin A1c (HbA1c) from baseline at week 16. Results Patients in the dapagliflozin group showed an adjusted decrease in HbA1c of −0.55% from baseline, whereas the placebo showed a marginal increase of 0.05%. The placebo-corrected mean change of HbA1c from baseline to week 16 in dapagliflozin was −0.60% (P < 0.0001). In addition, the placebo-corrected mean change of fasting plasma glucose and bodyweight from baseline to week 16 in the dapagliflozin group was −22.7 mg/dL (P < 0.0001) and −1.21 kg (P < 0.0001), respectively. The placebo-corrected mean daily insulin dose in the dapagliflozin group was numerically decreased (treatment difference: −0.72 IU/day; P = 0.0743). No major episodes or discontinuations as a result of hypoglycemia were reported during the study period. Conclusions Dapagliflozin used as add-on treatment to insulin therapy showed significantly greater reduction of HbA1c, fasting plasma glucose and bodyweight without severe hypoglycemia compared with the placebo at week 16. These results show the clinical benefit of prescribing dapagliflozin for Japanese patients with insufficient glycemic control even with insulin therapy.

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

Associations between graphemes and colours in a nonsynaesthetic Japanese population were investigated. Participants chose the most suitable colour from 11 basic colour terms for each of 40 graphemes from the four categories of graphemes used in the Japanese language (kana characters, English alphabet letters, and Arabic and kanji numerals). This test was repeated after a three-week interval. In their responses, which were not as temporally consistent as those of grapheme–colour synaesthetes, participants showed biases and regularities that were comparable to those of synaesthetes reported in past studies. Although it has been believed that only synaesthetes, and not nonsynaesthetes, tended to associate graphemes with colours based on grapheme frequency, Berlin and Kay's colour typology, and colour word frequency, participants in this study tended in part to associate graphemes with colours based on the above factors. Moreover, participants that were nonsynaesthetes tended to associate different graphemes that shared sounds and/or meanings (e.g., Arabic and kanji numerals representing the same number) with the same colours, which was analogous to the findings in Japanese synaesthetes. These results support the view that grapheme–colour synaesthesia might have its origins in cross-modal association processes that are shared with the general population.