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BACKGROUND: Pediatric patients with eating disorders in a multicenter joint study on 11 facilities were enrolled and prospectively investigated to determine whether improvement in body weight, eating attitudes, and psychosocial factors in children with eating disorders would also improve depressive symptoms. METHODS: In this study, 91 patients were enrolled between April 2014 and March 2016. The severity of underweight was assessed using the body mass index-standard deviation score (BMI-SDS), eating behavior was assessed using the children's eating attitude test (ChEAT26), the outcome of childhood eating disorders was assessed using the childhood eating disorder outcome scale, and depressive symptoms were assessed using the Children's Depression Inventory (CDI) score. RESULTS: After 12 months of treatment, depressive symptoms were evaluated in 62 of the 91 cases where it was evaluated at the initial phase. There was no difference in background characteristics between the included patients and the 29 patients who dropped out. A paired-sample t-test revealed a significant decrease in CDI scores after 12 months of treatment (p < 0.001, 95% CI: 2.401-7.373) and a significant increase in the BMI-SDS (p < 0.001, 95% CI: - 2.41973-1.45321). Multiple regression analysis revealed that BMI-SDS and ChEAT26 scores at the initial phase were beneficial in CDI recovery. In addition, BMI-SDS at the initial phase was useful for predicting BMI-SDS recovery after 12 months of treatment. CONCLUSIONS: Depressive symptoms in children with eating disorders improved with therapeutic intervention on body weight and eating attitudes. TRIAL REGISTRATION: The Clinical Trial Number for this study is UMIN000055004.

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BACKGROUND: A change in the timing of the Bacillus Calmette-Guérin (BCG) vaccination among infants in Japan appears to be associated with an increase in the incidence rate of latent tuberculosis infection (LTBI). METHODS: Data on both active and latent tuberculosis (TB) infections from 2007 to 2019, which were reported by the Japan Anti-Tuberculosis Association, were statistically analyzed by comparing TB incidence rates in 2007-2012 and 2013-2019. RESULTS: Although the incidence rate for active TB disease did not statistically increase nor decrease in the infant age group for either sex (and in fact decreased for some of the other age groups), the incidence rates of LTBI for both sexes were increased in the infant age group, while the incidence rates decreased in the other age groups. Between 2007 and 2012, the incidence rate of LTBI in females was statistically greater than those of males in the 1-4-year-old age group. From 2013 to 2019, the incidence rates of females were greater than those of males in both the infant and 1-4-year-old age groups, suggesting a growing preponderance of infections among female children in the youngest age groups. CONCLUSION: It may be that the change of BCG vaccination timing in Japan which took place in 2013 affected the infant incidence rate of LTBI, with a more prominent effect on females than males. In order to control TB infection, the ramifications of a change in vaccination timing therefore need careful exploration, as one such change appears associated with increased numbers of infants with LTBI, with disproportionate effects on females.

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ABSTRACT: Age-related narrowing of the visual field is observed in the elderly, which leads to reduced cognitive and psychomotor functions. The aim of the present cross-sectional study was to determine the influence of aging on the visual field for color vision in humans, with respect to angular thresholds for object detection and color detection.The subjects were divided into the elderly group (mean 76.1-year-old [70-89]) and the control group (25.2 [18-47]). Visual fields for different colors (blue, green, yellow, and red) were measured by manual kinetic perimetry and evaluated in terms of 2 measures of visual-field width: angular thresholds for object detection and those for color detection.While angular thresholds for object detection were significantly wider than those for color detection in the control group (P < .001), there was no difference in the elderly group (P = .06). Moreover, angular thresholds for object detection were significantly wider in the control group than in the elderly group (P = .019), but angular thresholds for color detection were not significantly different between the 2 groups (P = .903).The observed age-related changes in angular thresholds for object detection in color vision may reflect an age-related reduction in rod function. Stable cone function might explain the preserved angular thresholds for color detection in the elderly.

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This paper proposes a method for deriving interpretable common factors based on canonical correlation analysis applied to the vectors of common factors and manifest variables in the factor analysis model. First, an entropy-based method for measuring factor contributions is reviewed. Second, the entropy-based contribution measure of the common-factor vector is decomposed into those of canonical common factors, and it is also shown that the importance order of factors is that of their canonical correlation coefficients. Third, the method is applied to derive interpretable common factors. Numerical examples are provided to demonstrate the usefulness of the present approach.

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Sexually transmitted diseases (STDs) are causes of public health burden globally. The purpose of this study is to document age-specific and sex-related changes in the morbidity of four representative STDs in children. Japanese national surveillance data from 1999 to 2017 on morbidities of the following four STDs were analyzed by age and sex: Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), condylomata acuminate (CA), and genital herpes simplex virus (GHSV). The morbidities of males and females in each age group were compared through the male-to-female morbidity (MFM) ratios. The MFM ratios were not different from one in infants, less than one in children, and greater than one after puberty in all four STDs. The reversal of MFM ratio less than 1 to greater than 1 for NG infection was observed between 10-14 and 15-19 year of age, i.e., during the puberty, while that for GHSV infection was observed between 35-39 and 40-44 year of age, i.e., during adulthood. In conclusion, the morbidities of the four STDs were similar between the sexes in infants, and were higher in female children than in male children, while the morbidities in all four diseases were higher in men after puberty.

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OBJECTIVE: The number of patients with type 2 diabetes has increased in Japan, and type 2 diabetes has attracted attention as a risk factor for asthma. However, the risk factors for the development of asthma in patients with type 2 diabetes have not been determined. This study was performed to clarify whether visceral fat accumulation (VFA) and insulin resistance are risk factors for the development of asthma in patients with type 2 diabetes. MATERIALS AND METHODS: A cross-sectional study was conducted. The study group comprised 15 patients with type 2 diabetes with asthma, and the control group comprised 145 patients with type 2 diabetes without asthma. Their fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. Their glucose status was assessed by measuring the fasting plasma glucose (FPG) concentration, fasting immunoreactive insulin concentration, homeostasis model assessment (HOMA) index, and hemoglobin A1c concentration. RESULTS: Among patients with type 2 diabetes, VFA was significantly greater in patients with asthma than those without asthma (P < 0.0001). The FPG concentration, fasting immunoreactive insulin concentration, and HOMA index were higher in patients with asthma than those without asthma (P < 0.05, P < 0.0001, and P < 0.0001, respectively). Multiple logistic regression analysis showed that VFA and the HOMA index were significantly associated with asthma in patients with type 2 diabetes (odds ratio, 1.78; 95% confidence interval, 1.31-3.89; P = 0.0115 and odds ratio, 3.65; 95% confidence interval, 1.37-7.85; P = 0.0078, respectively). CONCLUSIONS: Our data suggest that VFA and insulin resistance are associated with the development of asthma in patients with type 2 diabetes.

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BACKGROUND/AIM: Re-employment is the goal of rehabilitation for many patients after stroke. This study retrospectively examined previously employed stroke survivors who were unable to return to work at time of discharge from hospital and identified factors which were correlated with successful re-employment following a rehabilitation programme involving occupational therapy at a support facility. Factors correlated with reactivation of drivers' licence after stroke were also investigated. METHODS: Participants were 150 post-stroke patients who were discharged from a support facility for persons with disabilities from April 2011 to March 2016. Data on patients' sociodemographic information, activities of daily living, and physical functions had been recorded at the time of admission into the facility. Employment status was recorded at discharge. Data were collected retrospectively in July 2017 from the medical records. Logistic regression models were prepared to examine factors correlated with successful re-employment and reactivation of drivers' licence after occupational therapy. RESULTS: A stepwise logistic regression model revealed that the following four factors were significantly correlated with successful re-employment: (i) the dressing-lower body item in the Functional Independence Measure (P < 0.001), (ii) the grooming item in the Functional Independence Measure (P = 0.002), (iii) marital status (P = 0.007), and (iv) the problem-solving item in the Functional Independence Measure (P = 0.028). Another stepwise logistic regression model revealed that the factors were significantly correlated with successful reactivation of drivers' licence: (i) the problem-solving item in the Functional Independence Measure (P = 0.002), (ii) the dressing-lower body item in the Functional Independence Measure (P = 0.011) and (iii) the residence area (P = 0.038). CONCLUSION: A single-centre retrospective study demonstrated several significant correlates of successful re-employment and reactivation of drivers' licence after stroke following rehabilitation training which employs occupational therapy to target skills critical for employment.

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AIM: Severe tooth loss and swallowing dysfunction occur more frequently in dependent older adult populations. Poor oral health and functional status are expected to have a negative impact on general health. We examined whether mortality is related to the number of teeth and swallowing function in dependent older Japanese individuals receiving home care services. METHODS: Older adults aged ≥65 years who were receiving home care were included. The planned follow-up period was 3 years. Baseline data on the number of teeth, swallowing function, nutritional status, cognitive ability and activities of daily living were collected. RESULTS: A total of 259 participants (mean age 85.0 ± 7.7 years) were enrolled. The mean length of follow up was 26.2 months. Severe tooth loss (≤9 present teeth) and swallowing dysfunction were observed in 68.0% and 32.0% of the participants, respectively. Cox's proportional hazards regression model showed that participants with both ≤9 teeth and swallowing dysfunction were at a higher risk of mortality compared with those with both ≥10 teeth and normal swallowing function (hazard ratio 2.89, 95% confidence interval 1.22-6.83). A significant interaction among severe tooth loss, swallowing dysfunction and mortality risk was observed. CONCLUSIONS: Severe tooth loss and swallowing dysfunction were associated with increased mortality. The present study suggests that the maintenance of oral health and swallowing function has a positive effect on general health. Therefore, attention should be given to both tooth loss and swallowing function in dependent older adult populations. Geriatr Gerontol Int 2018; 18: 873-880.

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In factor analysis, factor contributions of latent variables are assessed conventionally by the sums of the squared factor loadings related to the variables. First, the present paper considers issues in the conventional method. Second, an alternative entropy-based approach for measuring factor contributions is proposed. The method measures the contribution of the common factor vector to the manifest variable vector and decomposes it into contributions of factors. A numerical example is also provided to demonstrate the present approach.

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Pigmented cosmetic dermatitis-like (Riehl's melanosis-like) pigmentation was reported in three of 27 patients with primary Sjögren's syndrome. But case reports of such eruptions are rare. We describe three cases of such eruptions associated with primary Sjögren's syndrome or anti-SSA antibody and possible associations with specific types of human leukocyte antigen (HLA) and infiltrating lymphocytes. These middle-aged Japanese women had reticular facial pigmentation and histopathological examination revealed interface dermatitis, melanophages, and dense lymphocytic infiltration around hair follicles and sweat ducts. HLA typing revealed common antigenic equivalents or genetic typing of HLA-A2, DR52, DPA1(02:02) and DPB1(05:01). Immunohistochemical staining revealed major subsets of T cells to be CD8 and CD45RO. Some Foxp3- and few IL17-positive cells were found in strong contrast to the major CD4 subset of infiltrated T cells in annular erythema associated with Sjögren's syndrome. Apparently, our patients' pigmentation represented a specific etiology associated with primary Sjögren's syndrome or anti-SSA antibody.

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We performed skin cancer screenings for 2 or 3 days annually from 2006 through 2013 in Oita Prefecture, Japan. Screening of approximately 3000 people in total allowed us to identify and treat several skin cancers, including five cases of malignant melanoma, four of squamous cell carcinoma, 16 of basal cell carcinoma, 11 of Bowen's disease, 17 of actinic keratosis, one of extramammary Paget's disease and one of metastatic breast carcinoma. The sensitivity and specificity for the category defined by an identified lesion associated with risk of cancer and requiring further examination (category C) were 92.7% and 95%, respectively. We cannot estimate the outcome of our skin cancer screenings in terms of cancer mortality because of the small number of subjects examined and the brief follow-up period. However, we did estimate the effectiveness of these screenings in terms of stages or sizes of cancerous lesions. The relative numbers of subjects with malignant melanoma at various clinical stages, identified during skin cancer screenings and during a routine visit to our hospital, were significantly different. We also compared, statistically, the sizes of lesions in Bowen's disease that were found during cancer screenings and during a direct visit to our hospital. The former lesions were smaller than the latter. Our data suggest the benefits of our skin cancer screenings and the importance of campaigns and education to encourage people to visit dermatologists for the detection of skin cancers at an early stage.

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BACKGROUND: Human leukocyte antigen (HLA) genotypes in lamotrigine -induced (LTG-induced) cutaneous adverse drug reactions (cADRs) have been described in several reports but controversy remains even for a given ethnic group. We attempted to clarify a possible association between LTG-induced cADRs and HLA alleles in Japanese patients. METHOD: Sixteen subjects, including eight patients with LTG-induced cADRs and eight LTG-tolerant controls were included in this study. All eight patients with LTG-induced cADRs gave positive results in a drug-induced lymphocyte stimulation test (DLST) with LTG. We performed HLA-typing for HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1, using PCR with sequence-specific oligonucleotide probes and multiple analyte profiling (xMAP) technology (Luminex System; Luminex Corporation, Austin, TX). We examined differences between allele frequencies in our two groups of subjects and the allele frequencies in the general Japanese population. RESULTS: The frequencies of HLA-DRB1*0405, and HLA-DQB1*0401 alleles were higher in our LTG-cADRs patients than the reference frequencies in the general Japanese population. We also detected HLA-DQA1*0303 frequently in our LTG-cADRs patients, but data for this allele in the Japanese population was not available. Our observation was presumably due to the linkage disequilibrium among the three alleles. The haplotype frequency of HLA-DRB1*0405, DQB1*0401 and DQA1*0303 in our LTG-cADRs subjects was also different from the corresponding haplotype frequency in the database for the Japanese population and the difference was statistically significant. One patient with the HLA-DRB1*0405, -DQB1*0401 and DQA1*0303 haplotype was safely re-treated with LTG after results of a DLST with LTG ceased to be positive about 4 months after discontinuation of LTG. LIMITATIONS: Our analysis included only 16 patients. Associations between LTG-induced cADRs and specific HLA loci will have to be confirmed in larger studies. CONCLUSIONS: LTG-induced cADRs are associated with HLA-DRB1*0405, -DQB1*0401 and -DQA1*0303.

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Dental plaque is a dynamic microbial biofilm ecosystem that comprises hundreds of species including difficult-to-cultivate bacteria. We observed the assembly of a plaque bacterial community through 16S rRNA gene analysis. Plaque samples that accumulated on a hydroxyapatite disk for 1, 2, 3, 4, 5, and 7 days with saliva on day 0 were collected from 19 young adults using a removable resin splint. Quantitative PCR analysis showed that the total bacterial amount gradually increased and reached a plateau on day 4. Barcoded pyrosequencing analysis revealed that the microbial richness and diversity particularly increased between days 5 and 7. A principal coordinate analysis plot based on unweighted UniFrac showed the community assembly in a time-related manner, which became increasingly similar to the salivary microbiota. Facultative anaerobic bacteria such as Streptococcus, Neisseria, Abiotrophia, Gemella, and Rothia were predominant in the plaque bacterial community in the earlier days, whereas obligate anaerobes, such as Porphyromonas, Fusobacterium, Prevotella, and Capnocytophaga showed increased dominance on later days. UniFrac analysis also demonstrated that dental caries experience had a significant effect on the assembly process. Our results reveal the development pattern of the plaque bacterial community as well as the inter-individual differences associated with dental caries experience.

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AIM: The purpose of this prospective cohort study was to investigate whether body mass index (BMI) and oral health behaviour are related to changes in periodontal status in Japanese university students. MATERIALS AND METHODS: Students (n = 224) who were interested in receiving oral health examinations before entering university and before graduation were included in the analysis. Subjects were investigated regarding the correlations of oral health behaviours and increases in BMI with the percentage of bleeding on probing (%BOP) and Community Periodontal Index (CPI) scores as indicators of changes in periodontal status. RESULTS: The risk of increased %BOP was associated with the non-use of dental floss (adjusted odds ratio [OR]: 3.11; 95% confidence interval [CI]: 1.31-7.37; p < 0.05), whereas the risk of increased CPI score was associated with increases in BMI (OR: 1.95; 95% CI: 1.05-3.65; p < 0.05) and simplified oral hygiene index score (OR: 2.28; 95% CI: 1.23-4.22; p < 0.01). CONCLUSION: Increases in BMI were associated with worsening of periodontal status, defined as increased CPI score in Japanese university students, whereas lack of inter-dental cleaning was associated with exacerbated gingival bleeding.

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BACKGROUND: Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. PATIENTS AND METHODS: The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. RESULTS: A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. CONCLUSION: Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.

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AIMS: Periodontal disease and metabolic syndrome (MS) are more prevalent in males than in females. However, whether there is a gender difference in the association between these health conditions has not yet been investigated. This study examined the gender difference in this association, considering the definition of periodontal disease. MATERIALS AND METHODS: We recruited 1040 males and 1330 females, aged ≥40 years, with at least ten teeth from subjects of the 2007 Hisayama health examination. We performed a logistic regression analysis with various definitions of periodontal disease the dependent variable and MS as the independent variable. Following the analysis, the data were reanalysed with the structural equations model. RESULTS: The logistic regression analysis suggested a stronger association between periodontal disease and MS in females than that in males when periodontal disease was more severely defined. When we constructed the structural equations model in each gender, the model showed a good fit to the data of females, suggesting the association between periodontal disease and MS in females, but not in males. CONCLUSIONS: Gender differences seem to exist in the association between periodontal disease and MS; MS might show a stronger association with periodontal disease in females than in males.

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This study evaluated the effects of weak transcranial direct current stimulation (tDCS), a new non-invasive brain stimulation technique, on amygdala-kindled rats. The seizure severity, i.e. seizure stage, afterdischarge duration (ADD), and AD threshold (ADT) in the animals were measured one day after the last cathodal tDCS session, comparing with those of pre-treatment controls. Furthermore, the effects of cathodal tDCS on cognitive function were also studied by a water maze test (WMT) two days after the last tDCS session. Cathodal tDCS treatment significantly improved the seizure stage and decreased ADD together with elevated ADT one day after the last tDCS session. The treatment also showed significant improvement in the performance of WMT. The findings suggest that cathodal tDCS has anticonvulsive after-effects last at least for one day on the amygdala-kindled rats and positively affects cognitive performance.

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BACKGROUND: In the rodent and human fetus, a diurnal cortisol rhythm is observed that is entrained in antiphase to the maternal rhythm. However, after birth, the adrenal circadian rhythm becomes unsynchronized with the clock time, and an adult-type, 24-h rhythm is observed only after a few months. Little is known about when and how the fetal adrenal circadian rhythm is synchronized with the day-night cycle. METHODS: To investigate the function of adrenal circadian clock in the newborn infant, eight serial saliva samples were collected every 3 h over 24 h (starting at 0900 h) in 27 newborn infants. RESULTS: Cortisol levels were higher during the period 1500 to earlier than 2100 h than during 0900 to earlier than 1500 h and 0300 to earlier than 0900 h (both P < 0.05). Salivary cortisol levels collected during 0 to <6, 6 to <12, and 12 to <18 hours after the clock time at birth (birth time) were higher than those collected during 18 to <24 hours after the birth time (P < 0.005, 0.05, and 0.05, respectively). The acrophase of salivary cortisol was linearly correlated with the birth time within the first 5 d of life (P < 0.005) but not thereafter. CONCLUSION: In the newborn infant, diurnal increase in cortisol was observed in the late afternoon and in correspondence with the birth time. The adrenal circadian rhythm acquired in utero may be reentrained by endocrinological events at birth. Such complex regulation of the adrenal circadian clock may inhibit a swift synchronization of the circadian clock to the day-night rhythm.

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BACKGROUND: To prevent and control infectious diseases, it is important to understand how sex and age influence morbidity rates, but consistent clear descriptions of differences in the reported incidence of infectious diseases in terms of sex and age are sparse. METHODS AND FINDINGS: Data from the Japanese surveillance system for infectious diseases from 2000 to 2009 were used in the analysis of seven viral and four bacterial infectious diseases with relatively large impact on the Japanese community. The male-to-female morbidity (MFM) ratios in different age groups were estimated to compare incidence rates of symptomatic reported infection between the sexes at different ages. MFM ratios were >1 for five viral infections out of seven in childhood, i.e. male children were more frequently reported as infected than females with pharyngoconjunctival fever, herpangina, hand-foot-and-mouth disease, mumps, and varicella. More males were also reported to be infected with erythema infectiosum and exanthema subitum, but only in children 1 year of age. By contrast, in adulthood the MFM ratios decreased to <1 for all of the viral infections above except varicella, i.e. adult women were more frequently reported to be infected than men. Sex- and age-related differences in reported morbidity were also documented for bacterial infections. Reported morbidity for enterohemorrhagic Escherichia coli infection was higher in adult females and females were reportedly more infected with mycoplasma pneumonia than males in all age groups up to 70 years. CONCLUSIONS: Sex-related differences in reported morbidity for viral and bacterial infections were documented among different age groups. Changes in MFM ratios with age may reflect differences between the sexes in underlying development processes, including those affecting the immune, endocrine, and reproductive systems, or differences in reporting rates.

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