Intraindividual variation in histone acetylation and its impact on autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITDs), such as Graves' disease (GD) and Hashimoto's disease (HD), are organ-specific autoimmune diseases. Histone acetylation, especially that of histone H3, is an epigenetic mechanism that regulates gene expression and is associated with the development of autoimmune diseases. However, physiological variations in histone acetylation are not yet clear, and we believe that physiological variations should be examined prior to analysis of the role of histone H3 in the pathogenesis of AITDs. In this study, we analyzed histone H3 acetylation levels in peripheral blood mononuclear cells (PBMCs) using a histone H3 total acetylation detection fast kit. Blood samples were collected before meals, between 8:30-9:00 am, daily for 10 weeks to evaluate the daily variation. At 4 days, blood was also collected before meals three times a day (at 8:30-9:00, 12:30-13:00, and 16:30-17:00) to evaluate circadian variation. Then, histone H3 acetylation levels were evaluated in AITD patients to clarify the association with the pathogenesis of AITD. Although we could not find a common pattern of circadian variance, we observed daily variation in histone H3 acetylation levels, and their coefficient of variances (CVs) were approximately 48.3%. Then, we found that histone H3 acetylation levels were significantly lower in GD and HD patients than in control subjects and these differences were larger than the daily variation in histone acetylation. In conclusion, histone H3 acetylation levels were associated with the development of AITD, even allowing for daily variation.

Needs assessment of caregivers of children with disabilities in resource-limited settings.

Objective: This study aimed to identify and classify the needs of caregivers of children with disabilities living in resource-limited settings and develop a framework for need assessment. Participants and Methods: This study was conducted in the Maha Sarakham Province, Thailand, with 15 caregivers caring for children with disabilities recruited from hospitals, the Association for the Disabled, and primary health centers. Semi-structured interviews were conducted in local dialects, recorded, transcribed, converted into standard Thai, and then into English for thematic analysis. Meaning units corresponding to caregivers' needs were extracted, interpreted, coded, and hierarchically organized into subcategories by comparing similarities and differences among the extracted codes. The subcategories were further grouped and abstracted into categories, and then domains of caregivers' needs were formed. Results: Nineteen categories were identified across five domains of caregivers' needs: health and medical, welfare, educational, social, and informational. Although basic medical treatment was covered, specific support, such as referral to a specialist, rehabilitation, or psychological support, was limited. Financial support and relief from the care burden are the main welfare needs. Educational needs were identified to provide knowledge to children and to offer respite to their caregivers. Social needs revealed ethical problems that arose because of strong rural community ties, making it difficult to maintain privacy. Informational needs were intertwined with the other four domains. In rural areas, where parents of children with disabilities migrate to cities to find work, the special needs of grandparents who were primary caregivers of the children needed to be addressed. Conclusion: This study provides a conceptual framework for comprehensive needs assessment and policy development for caregivers of children with disabilities living in resource-limited settings.

Association of IFNG gene methylation in peripheral blood cells with the development and prognosis of autoimmune thyroid diseases.

The intractability of Graves' disease (GD) and the severity of Hashimoto's disease (HD) vary among patients. Both genetic and environmental factors may be associated with their prognoses. To clarify the role of methylation of the IFNG gene in the pathogenesis and prognosis of (AITDs), we examined interferon gamma (IFNG) methylation levels at various CpG sites and genotyped IFNG +874 A/T and +2109 C/T polymorphisms. We analyzed methylation 59 patients with HD, 57 patients with GD and 26 healthy volunteers by pyrosequencing. We genotyped IFNG gene polymorphisms from 207 patients with GD, 208 patients with HD, and 102 healthy controls. The methylation levels of IFNG -54 CpG were higher in patients with intractable GD than in those with GD in remission, but there was no difference between patients with severe and mild HD. In carriers of IFNG +2109 T (CT + TT) (85.5% in controls), the -54 CpG methylation levels were significantly higher in patients with intractable GD than in those with GD in remission. On the other hand, in carriers of IFNG +2109 CC, the -4293 CpG methylation levels were higher in intractable GD patients. The methylation levels of IFNG -54 CpG and -4293 CpG were negatively correlated with the age in HD, especially severe HD, patients and GD patients, respectively. There was no circadian variation but considerable daily variation in the methylation levels of IFNG -54 CpG. In conclusion, both the methylation levels of CpG sites and the functional polymorphisms in the IFNG gene were associated with the pathogenesis and prognosis of AITD, especially with GD intractability.

Methylation levels of the TNFA gene are different between Graves' and Hashimoto's diseases and influenced by the TNFA polymorphism.

Graves' disease (GD) and Hashimoto's disease (HD) are different pathological types of autoimmune thyroid diseases (AITDs). However, the epigenetic differences between these diseases have not been elucidated. DNA methylation is one of the primary epigenetic modifications that reflect environmental influences on gene expression. In this study, we evaluated the methylation status of six CpG sites in the TNFA promoter using pyrosequencing and analyzed the data in combination with functional polymorphisms (-1031 T/C and +123 C/T) in the TNFA gene to clarify the role of gene methylation on the prognosis of AITDs. We examined the methylation pattern in 52 patients with GD, 60 patients with HD, and 29 healthy controls by pyrosequencing. Additionally, we also genotyped the polymorphisms from 163 patients with GD, 152 patients with HD, and 94 healthy controls using the restriction fragment length polymorphism (RFLP) method. Each proportion of subjects with low methylation of the -72 CpG site (≤11.9%), low methylation of the -49 CpG site (≤15.5%), and low methylation of the -38 CpG site (≤8.9%) was significantly increased in the groups with high concentration of TNF-α (≥0.134 pg/mL). The methylation level of the -72 CpG site was significantly higher in GD cases (10.7 ± 4.9%) than in healthy controls (6.8 ± 3.9%). The methylation level of the -49 and -38 CpG sites were significantly higher in patients with GD in remission (20.5 ± 9.5%, 17.6 ± 8.0%, respectively) than in healthy controls (13.0 ± 7.6%, 7.9 ± 7.3%, respectively). The frequency of the TNFA - 1031C carrier (CT + CC) is correlated with higher TNF-α production and was significantly higher in GD (35.0%) and HD (39.5%) cases than in controls (19.1%). In the subjects with the TNFA - 1031C carrier (CT + CC), the methylation level of the -72 CpG site was significantly higher in GD (11.5 ± 5.7%) than in HD (6.0 ± 3.4%). However, there was no difference between GD and HD in patients with the TT genotype. Cumulatively, our data indicate the methylation levels of CpG sites in the TNFA gene may be related to the difference between GD and HD in AITDs and may be influenced by the TNFA gene polymorphism.

Development of health literacy scale among Brazilian mothers in Japan.

Japanese-Brazilians were the third largest immigrant group in Japan in 2011. Their health issues have caused concern, as their limited language made them vulnerable by hindering access to health services. Upon considering child health, mothers' health literacy (HL) is very important. This study aimed to develop a health literacy scale among Brazilian mothers (HLSBM) in Japan. Questionnaires in Portuguese were distributed to 1474 mothers from December 2011 to March 2012. Among 698 collected, 558 questionnaires were analyzed. We prepared 29 candidate items for HLSBM based on Nutbeam's concept of functional, interactive and critical literacy. The dimensional structure was determined statistically using confirmatory factor analysis. Validity was also analyzed by Pearson's correlation with Ishikawa's scale and Kendall's coefficient of concordance among researchers. Cronbach's α coefficients were calculated to examine internal consistency. The confirmatory factor analysis revealed a two-factor model (five items for basic literacy and five items for critical literacy) with sufficient goodness of fit (GFI 969, AGFI 945, NFI 959, CFI 972, RMSEA 060). The internal consistency values of the total score, basic and critical literacy sub-scales were 0.819, 0.889 and 0.667, respectively. Kendall's coefficient of concordance showed good agreement of researchers (p < 0.001). Pearson's correlation coefficients with Ishikawa's scale were 0.554 for total score, 0.446 for basic literacy and 0.472 for critical literacy. The HLSBM consisting of two factors was confirmed to be valid and reliable. The HLSBM must be useful for understanding this vulnerable group's health literacy and its associated factors.