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AIM: To assess the safety/tolerability, efficacy and pharmacokinetics of once-daily, 600-µg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher. MATERIALS AND METHODS: This phase I, randomized, double-blind, placebo-controlled study (NCT04208620) enrolled patients to receive subcutaneous cotadutide at an escalating dose to determine the highest tolerated clinical dose (Cohort 1), then applied in Cohort 2. The primary endpoint was safety, including treatment-emergent adverse events (TEAEs); secondary endpoints included glycaemic control and body weight. RESULTS: Sixteen patients were randomly allocated to receive cotadutide or placebo in a 3:1 ratio. All patients were Asian, 62.5% were male, and the median age and body mass index were 60 years and 27.2 kg/m2 , respectively. Through the follow-up period of the study, 11/12 (91.7%) patients in the cotadutide group experienced a TEAE versus 1/4 (25.0%) patients in the placebo group. All TEAEs were mild, except for one moderate event. There were no deaths, serious TEAEs or TEAEs leading to study discontinuation. Gastrointestinal-related events were the most common TEAEs. Cotadutide-treated patients achieved significantly improved 7-day mean glucose measured by continuous glucose monitoring; the 7-day mean (standard deviation) at the end of treatment (day 70) was 112.23 (20.79) versus 206.85 (3.62) mg/dL for placebo. Mean respective changes in HbA1c were -1.13% (0.64%) and -0.17% (0.65%); and mean percentage changes in body weight were -6.93% (3.44%) and -1.23% (1.20%). CONCLUSIONS: Cotadutide was well tolerated at doses up to 600 µg; efficacy versus placebo for weight loss and glycaemic control was shown.
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Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Femenino , Humanos , Masculino , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea , Índice de Masa Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Pueblos del Este de Asia , Hemoglobina Glucada , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/uso terapéutico , Resultado del Tratamiento , Persona de Mediana Edad , Inyecciones Subcutáneas , Relación Dosis-Respuesta a DrogaRESUMEN
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.
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Pueblos del Este de Asia , Encuestas y Cuestionarios , Prejuicio de Peso , Adulto , Humanos , Masculino , Estudios Transversales , Psicometría , Reproducibilidad de los Resultados , Autoimagen , Estigma Social , FemeninoRESUMEN
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.
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Diabetes Mellitus Tipo 2 , Receptores de Glucagón , Adulto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Glucagón , Péptido 1 Similar al Glucagón , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón/efectos adversos , Humanos , Hipoglucemiantes/efectos adversos , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Sobrepeso/complicaciones , Sobrepeso/tratamiento farmacológico , PéptidosRESUMEN
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.
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Diabetes Mellitus Tipo 1 , Compuestos de Bencidrilo/efectos adversos , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Método Doble Ciego , Quimioterapia Combinada , Glucósidos , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/efectos adversos , Insulina/uso terapéutico , Japón/epidemiología , Método Simple Ciego , Resultado del TratamientoRESUMEN
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.
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Percepción de Color , Trastornos de la Percepción , Adulto , Humanos , Estudios Longitudinales , Reconocimiento Visual de Modelos , Estimulación Luminosa , SinestesiaRESUMEN
Grapheme-color synesthetes experience graphemes as having a consistent color (e.g., "N is turquoise"). Synesthetes' specific associations (which letter is which color) are often influenced by linguistic properties such as phonetic similarity, color terms ("Y is yellow"), and semantic associations ("D is for dog and dogs are brown"). However, most studies of synesthesia use only English-speaking synesthetes. Here, we measure the effect of color terms, semantic associations, and non-linguistic shape-color associations on synesthetic associations in Dutch, English, Greek, Japanese, Korean, Russian, and Spanish. The effect size of linguistic influences (color terms, semantic associations) differed significantly between languages. In contrast, the effect size of non-linguistic influences (shape-color associations), which we predicted to be universal, indeed did not differ between languages. We conclude that language matters (outcomes are influenced by the synesthete's language) and that synesthesia offers an exceptional opportunity to study influences on letter representations in different languages.
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Percepción de Color , Lenguaje , Trastornos de la Percepción , Color , Humanos , SinestesiaRESUMEN
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) <25.0 and ≥25.0 kg/m2 was evaluated in a subgroup analysis. RESULTS: In total, 151 patients received 5 mg (n = 76) or 10 mg (n = 75) dapagliflozin once daily for 52 weeks. Adverse events were observed in 88.2% and 73.3% of patients in the 5 and 10 mg dapagliflozin groups, respectively. Severe hypoglycaemia was reported in 2.6% (n = 2) and 6.7% (n = 5) of patients, and diabetic ketoacidosis in 2.6% (n = 2) and 1.3% (n = 1) of patients in the 5 and 10 mg dapagliflozin groups, respectively. The adjusted mean (95% confidence interval) changes in glycated haemoglobin at week 52 were -0.33% (-0.50, -0.15) and -0.36% (-0.53, -0.18) in the 5 and 10 mg dapagliflozin groups, respectively. There were no differences in efficacy parameters when stratified by BMI. CONCLUSIONS: This study demonstrated the long-term safety and tolerability of dapagliflozin added to insulin therapy in Japanese patients with inadequately controlled T1DM.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Compuestos de Bencidrilo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucósidos , Humanos , Hipoglucemiantes/efectos adversos , Japón/epidemiologíaRESUMEN
The empathizing-systemizing model describes human cognitive style using empathizing (the drive to identify another's mental state and respond appropriately) and systemizing (the drive to assess or construct rule-based systems). 'Brain type' was envisioned to explain individual differences in cognitive style based on the discrepancy of the two drives. In this model, individuals with autism spectrum disorder (ASD), a neurodevelopmental disorder, have extremely stronger systemizing. Revealing the underlying mechanisms of individual differences in cognitive style might contribute to elucidation of the pathology of ASD. We used voxel-based morphometry to compare the brain structures among the brain types (those who have stronger empathizing, those who have equally stronger drive to both, and those who have stronger systemizing) in 207 healthy children (age range: 5-15). Results showed that children with stronger systemizing had significantly greater grey matter volume of the right superior temporal gyrus (rSTG) than the others. The brain region, a distinctive brain structure of those with stronger systemizing, was overlapped with that of children with ASD. The rSTG is involved in detailed perceptual processing in social cognition, which is partially related to stronger systemizing. Our results contribute to elucidation of the underlying mechanisms of individual differences in cognitive style.
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Cognición , Sustancia Gris/diagnóstico por imagen , Percepción Social , Lóbulo Temporal/diagnóstico por imagen , Adolescente , Trastorno del Espectro Autista/psicología , Encéfalo , Mapeo Encefálico , Niño , Preescolar , Empatía , Femenino , Sustancia Gris/patología , Voluntarios Sanos , Humanos , Individualidad , Masculino , Tamaño de los Órganos , Personalidad , Conducta Social , Lóbulo Temporal/patología , PensamientoRESUMEN
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.
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Compuestos de Bencidrilo/farmacocinética , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucósidos/farmacocinética , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacocinética , Adulto , Compuestos de Bencidrilo/farmacología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Glucósidos/farmacología , Glucurónidos/sangre , Glucosuria/orina , Humanos , Japón , Masculino , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacologíaRESUMEN
Excessive internet use is shown to be cross sectionally associated with lower cognitive functioning and reduced volume of several brain areas. However, the effects of daily internet use on the development of verbal intelligence and brain structures have not been investigated. Here, we cross sectionally examined the effects of the frequency of internet use on regional gray/white matter volume (rGMV/rWMV) and verbal intelligence as well as their longitudinal changes after 3.0 ± 0.3 (standard deviation) years in a large sample of children recruited from the general population (mean age, 11.2 ± 3.1 years; range, 5.7-18.4 years). Although there were no significant associations in cross sectional analyses, a higher frequency of internet use was found to be associated with decrease of verbal intelligence and smaller increase in rGMV and rWMV of widespread brain areas after a few years in longitudinal analyses. These areas involve areas related to language processing, attention and executive functions, emotion, and reward. In conclusion, frequent internet use is directly or indirectly associated with decrease of verbal intelligence and development to smaller gray matter volume at later stages.
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Encéfalo/crecimiento & desarrollo , Inteligencia , Internet , Adolescente , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Estudios Transversales , Femenino , Sustancia Gris/anatomía & histología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/crecimiento & desarrollo , Humanos , Masculino , Tamaño de los Órganos , Seno Sagital Superior , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/crecimiento & desarrolloRESUMEN
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.
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Compuestos de Bencidrilo/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adulto , Compuestos de Bencidrilo/efectos adversos , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glucósidos/efectos adversos , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemiantes/efectos adversos , Japón/epidemiología , Masculino , Factores de Tiempo , Resultado del TratamientoRESUMEN
There is a vast amount of evidence from psychological studies that the amount of parent-child interaction affects the development of children's verbal skills and knowledge. However, despite the vast amount of literature, brain structural development associated with the amount of parent-child interaction has never been investigated. In the present human study, we used voxel-based morphometry to measure regional gray matter density (rGMD) and examined cross-sectional correlations between the amount of time spent with parents and rGMD among 127 boys and 135 girls. We also assessed correlations between the amount of time spent with parents and longitudinal changes that occurred a few years later among 106 boys and 102 girls. After correcting for confounding factors, we found negative effects of spending time with parents on rGMD in areas in the bilateral superior temporal gyrus (STG) via cross-sectional analyses as well as in the contingent areas of the right STG. We also confirmed positive effects of spending time with parents on the Verbal Comprehension score in cross-sectional and longitudinal analyses. rGMD in partly overlapping or contingent areas of the right STG was negatively correlated with age and the Verbal Comprehension score in cross-sectional analyses. Subsequent analyses revealed verbal parent-child interactions have similar effects on Verbal Comprehension scores and rGMD in the right STG in both cross-sectional and longitudinal analyses. These findings indicate that parent-child interactions affect the right STG, which may be associated with verbal skills.
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Encéfalo/crecimiento & desarrollo , Sustancia Gris/anatomía & histología , Relaciones Padres-Hijo , Adolescente , Encéfalo/anatomía & histología , Encéfalo/fisiología , Niño , Estudios Transversales , Femenino , Sustancia Gris/crecimiento & desarrollo , Humanos , Estudios Longitudinales , Masculino , Conducta VerbalRESUMEN
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.
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Envejecimiento/patología , Envejecimiento/fisiología , Corteza Cerebral/anatomía & histología , Hábitos , Plasticidad Neuronal/fisiología , Lectura , Sustancia Blanca/anatomía & histología , Adolescente , Corteza Cerebral/fisiología , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sustancia Blanca/fisiología , Adulto JovenRESUMEN
Television (TV) viewing is known to affect children's verbal abilities and other physical, cognitive, and emotional development in psychological studies. However, the brain structural development associated with TV viewing has never been investigated. Here we examined cross-sectional correlations between the duration of TV viewing and regional gray/white matter volume (rGMV/rWMV) among 133 boys and 143 girls as well as correlations between the duration of TV viewing and longitudinal changes that occurred a few years later among 111 boys and 105 girls. After correcting for confounding factors, we found positive effects of TV viewing on rGMV of the frontopolar and medial prefrontal areas in cross-sectional and longitudinal analyses, positive effects of TV viewing on rGMV/rWMV of areas of the visual cortex in cross-sectional analyses, and positive effects of TV viewing on rGMV of the hypothalamus/septum and sensorimotor areas in longitudinal analyses. We also confirmed negative effects of TV viewing on verbal intelligence quotient (IQ) in cross-sectional and longitudinal analyses. These anatomical correlates may be linked to previously known effects of TV viewing on verbal competence, aggression, and physical activity. In particular, the present results showed effects of TV viewing on the frontopolar area of the brain, which has been associated with intellectual abilities.
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Encéfalo/anatomía & histología , Encéfalo/crecimiento & desarrollo , Televisión , Aprendizaje Verbal , Adolescente , Niño , Estudios Transversales , Femenino , Lóbulo Frontal/anatomía & histología , Lóbulo Frontal/crecimiento & desarrollo , Sustancia Gris/anatomía & histología , Sustancia Gris/crecimiento & desarrollo , Humanos , Hipotálamo/anatomía & histología , Hipotálamo/crecimiento & desarrollo , Pruebas de Inteligencia , Estudios Longitudinales , Masculino , Corteza Prefrontal/anatomía & histología , Corteza Prefrontal/crecimiento & desarrollo , Tabique del Cerebro/anatomía & histología , Tabique del Cerebro/crecimiento & desarrollo , Sustancia Blanca/anatomía & histología , Sustancia Blanca/crecimiento & desarrolloRESUMEN
People are generally lean during childhood and show more variability in body sizes and shapes later in life. Cortical development generally correlates with body growth. However, in children cortical growth may be impaired with oversized body growth. Inverse correlations between body mass index (BMI) and brain volumes suggest that lean bodies may be associated with increased cortical volume. To clarify the positive effects of a lean body on a child's cortical development, we used MRI to measure brain structures longitudinally in 107 children and adolescents aged 5-16 years. The relationships between changes in BMI and cortical volumes during 3 years of development were investigated, while controlling for age, gender and intracranial volume changes. Voxel-based morphometry analyses revealed that an increase in the volume of the right posterior medial temporal lobe including the hippocampus and parahippocampal gyrus was associated with lower BMI increases. No correlations were observed between higher BMI increases and cortical volumes. Our results suggest that keeping a lean body or not getting fat during childhood can induce an increase in regional cortical volume rather than impair growth. This is the first longitudinal study showing positive effects of a lean body on cortical development in children.
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Índice de Masa Corporal , Corteza Cerebral/crecimiento & desarrollo , Desarrollo Infantil/fisiología , Hipocampo/crecimiento & desarrollo , Adolescente , Niño , Preescolar , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , MasculinoRESUMEN
Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech.
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Encéfalo/crecimiento & desarrollo , Encéfalo/fisiología , Desarrollo del Lenguaje , Fonética , Habla/fisiología , Adolescente , Mapeo Encefálico , Circulación Cerebrovascular/fisiología , Niño , Discriminación en Psicología/fisiología , Femenino , Humanos , Japón , Pruebas del Lenguaje , Imagen por Resonancia Magnética , MasculinoRESUMEN
Using the eye-tracking method, the present study depicted pre- and post-head processing for simple scrambled sentences of head-final languages. Three versions of simple Japanese active sentences with ditransitive verbs were used: namely, (1) SO1O2V canonical, (2) SO2O1V single-scrambled, and (3) O1O2SV double-scrambled order. First pass reading times indicated that the third noun phrase just before the verb in both single- and double-scrambled sentences required longer reading times compared to canonical sentences. Re-reading times (the sum of all fixations minus the first pass reading) showed that all noun phrases including the crucial phrase before the verb in double-scrambled sentences required longer re-reading times than those required for single-scrambled sentences; single-scrambled sentences had no difference from canonical ones. Therefore, a single filler-gap dependency can be resolved in pre-head anticipatory processing whereas two filler-gap dependencies require much greater cognitive loading than a single case. These two dependencies can be resolved in post-head processing using verb agreement information.
Asunto(s)
Movimientos Oculares/fisiología , Psicolingüística/métodos , Lectura , Adulto , Medidas del Movimiento Ocular , Femenino , Humanos , Japón , Masculino , Psicolingüística/instrumentación , Adulto JovenRESUMEN
In this study, we examined linear and curvilinear correlations of fractional anisotropy (FA), mean diffusivity (MD), and white matter volume with age by using brain structural and diffusion-tensor magnetic resonance imaging (MRI) in a large number of healthy children and voxel-based morphometry (VBM) and region-of-interest (ROI) analyses. We collected data by brain structural MRI in 246 healthy children, aged 5-18 years. FA and MD images were normalized using the normalization parameter of the corresponding structural MRI. Next, we analyzed the correlations between FA and age and between MD and age by estimating linear and logarithmic functions. We also analyzed the correlation between white matter volume and age by linear, quadratic, and cubic functions. Correlations between FA and age and between MD and age showed exponential trajectories in most ROIs in boys and girls, except for several fibers, such as the corpus callosum connecting the bilateral rectal gyri in boys. The correlation between white matter volume and age showed significant positive linear trajectories in most ROIs in boys and girls, except for a few fibers, such as the bilateral uncinate fasciculus. Additionally, maturational rates differed among major fibers, and in girls, the left superior longitudinal fasciculus, which connects the frontal and temporal lobes, showed a slower rate of maturation than other fibers. Our results may help to clarify the mechanisms of normal brain maturation from the viewpoint of brain white matter.
Asunto(s)
Encéfalo/crecimiento & desarrollo , Adolescente , Anisotropía , Niño , Preescolar , Imagen de Difusión Tensora , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Fibras Nerviosas MielínicasRESUMEN
We examined linear and curvilinear correlations of gray matter volume and density in cortical and subcortical gray matter with age using magnetic resonance images (MRI) in a large number of healthy children. We applied voxel-based morphometry (VBM) and region-of-interest (ROI) analyses with the Akaike information criterion (AIC), which was used to determine the best-fit model by selecting which predictor terms should be included. We collected data on brain structural MRI in 291 healthy children aged 5-18 years. Structural MRI data were segmented and normalized using a custom template by applying the diffeomorphic anatomical registration using exponentiated lie algebra (DARTEL) procedure. Next, we analyzed the correlations of gray matter volume and density with age in VBM with AIC by estimating linear, quadratic, and cubic polynomial functions. Several regions such as the prefrontal cortex, the precentral gyrus, and cerebellum showed significant linear or curvilinear correlations between gray matter volume and age on an increasing trajectory, and between gray matter density and age on a decreasing trajectory in VBM and ROI analyses with AIC. Because the trajectory of gray matter volume and density with age suggests the progress of brain maturation, our results may contribute to clarifying brain maturation in healthy children from the viewpoint of brain structure.
Asunto(s)
Envejecimiento , Encéfalo/crecimiento & desarrollo , Interpretación de Imagen Asistida por Computador/métodos , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: Long duration trial data for two-dose COVID-19 vaccines primary series' are uncommon due to unblinding and additional doses. We report one-year follow-up results from a phase 1/2 trial of AZD1222 (ChAdOx1 nCoV-19) in Japan. METHODS: Adults (n = 256) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age, 18-55 (n = 128), 56-69 (n = 86) and ≥70-year-old (n = 42), and randomized 3:1 to AZD1222 or placebo. Safety, immunogenicity, and exploratory efficacy data were collected until study Day 365. RESULTS: Safety was consistent with previous reports. In AZD1222 vaccinees, humoral responses against SARS-CoV-2 steadily declined over time. By Day 365, anti-SARS-CoV-2 spike-binding (spike) and receptor-binding domain (RBD) mean antibody titers remained above Day 15 levels and pseudovirus neutralizing antibodies were undetectable in many participants. CONCLUSIONS: AZD1222 is immunogenic and well tolerated in Japanese adults. Expected waning in anti-SARS-CoV-2 humoral responses was observed; spike and RBD antibody titers remained elevated. (ClinicalTrials.gov: NCT04568031).