Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases.

Genetic studies have revealed many variant loci that are associated with immune-mediated diseases. To elucidate the disease pathogenesis, it is essential to understand the function of these variants, especially under disease-associated conditions. Here, we performed a large-scale immune cell gene-expression analysis, together with whole-genome sequence analysis. Our dataset consists of 28 distinct immune cell subsets from 337 patients diagnosed with 10 categories of immune-mediated diseases and 79 healthy volunteers. Our dataset captured distinctive gene-expression profiles across immune cell types and diseases. Expression quantitative trait loci (eQTL) analysis revealed dynamic variations of eQTL effects in the context of immunological conditions, as well as cell types. These cell-type-specific and context-dependent eQTLs showed significant enrichment in immune disease-associated genetic variants, and they implicated the disease-relevant cell types, genes, and environment. This atlas deepens our understanding of the immunogenetic functions of disease-associated variants under in vivo disease conditions.

Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases.

OBJECTIVES: Despite the involvement of B cells in the pathogenesis of immune-mediated diseases (IMDs), biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated a large-scale repertoire catalogue of five B cell subsets of patients with IMDs. METHODS: We mapped B cell receptor regions from RNA sequencing data of sorted B cell subsets. Our dataset consisted of 595 donors under IMDs and health. We characterised the repertoire features from various aspects, including their association with immune cell transcriptomes and clinical features and their response to belimumab treatment. RESULTS: Heavy-chain complementarity-determining region 3 (CDR-H3) length among naïve B cells was shortened among autoimmune diseases. Strong negative correlation between interferon signature strength and CDR-H3 length was observed in naïve B cells and suggested the role for interferon in premature B cell development. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE). We developed a scoring system to quantify this skewing, and it positively correlated with peripheral helper T cell transcriptomic signatures and negatively correlated with the amount of somatic hyper mutations in plasmablasts, suggesting the association of extrafollicular pathway. Further, this skewing led to high usage of IGHV4-34 gene with 9G4 idiotypes in unswitched-memory B cells, which showed a prominent positive correlation with disease activity in SLE. Gene usage skewing in unswitched-memory B cells was ameliorated after belimumab treatment. CONCLUSIONS: Our multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases.

Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance.

OBJECTIVES: Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify immune cells that predict treatment resistance. METHODS: We isolated 18 peripheral blood immune cell subsets of 55 patients with RA requiring addition of new treatment and 39 healthy controls, and performed RNA sequencing. Transcriptome changes in RA and treatment effects were systematically characterised. Association between immune cell gene modules and treatment resistance was evaluated. We validated predictive value of identified parameters for treatment resistance using quantitative PCR (qPCR) and mass cytometric analysis cohorts. We also characterised the identified population by synovial single cell RNA-sequencing analysis. RESULTS: Immune cells of patients with RA were characterised by enhanced interferon and IL6-JAK-STAT3 signalling that demonstrate partial normalisation after treatment. A gene expression module of plasmacytoid dendritic cells (pDC) reflecting the expansion of dendritic cell precursors (pre-DC) exhibited strongest association with treatment resistance. Type I interferon signalling was negatively correlated to pre-DC gene expression. qPCR and mass cytometric analysis in independent cohorts validated that the pre-DC associated gene expression and the proportion of pre-DC were significantly higher before treatment in treatment-resistant patients. A cluster of synovial DCs showed both features of pre-DC and pro-inflammatory conventional DC2s. CONCLUSIONS: An increase in pre-DC in peripheral blood predicted RA treatment resistance. Pre-DC could have pathophysiological relevance to RA treatment response.

Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles.

OBJECTIVE: Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets. METHODS: We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls. RESULTS: HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling. CONCLUSION: This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.

Dysregulation of the gene signature of effector regulatory T cells in the early phase of systemic sclerosis.

OBJECTIVES: We evaluated flow-cytometric and transcriptome features of peripheral blood immune cells from early-phase (disease duration <5 years) SSc in comparison with late-phase SSc. METHODS: Fifty Japanese patients with SSc (12 early SSc cases and 38 late SSc cases) and 50 age- and sex-matched healthy controls were enrolled. A comparison of flow-cytometric subset proportions and RNA-sequencing of 24 peripheral blood immune cell subsets was performed. We evaluated differentially expressed genes (DEGs), characterized the co-expressed gene modules, and estimated the composition of subpopulations by deconvolution based on single-cell RNA-sequencing data. As a disease control, idiopathic inflammatory myositis (IIM) patients were also evaluated. RESULTS: Analysing the data from early and late SSc, fraction II effector regulatory T cell (Fr. II eTreg) genes showed a remarkable differential gene expression, enriched for genes related to oxidative phosphorylation. Although the flow-cytometric proportion of Fr. II eTregs was not changed in early SSc, deconvolution indicated expansion of the activated subpopulation. Co-expressed gene modules of Fr. II eTregs demonstrated enrichment of the DEGs of early SSc and correlation with the proportion of the activated subpopulation. These results suggested that DEGs in Fr. II eTregs from patients with early SSc were closely associated with the increased proportion of the activated subpopulation. Similar dysregulation of Fr. II eTregs was also observed in data from patients with early IIM. CONCLUSIONS: RNA-seq of immune cells indicated the dysregulation of Fr. II eTregs in early SSc with increased proportion of the activated subpopulation.

SAPHO syndrome and pustulotic arthro-osteitis.

Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10-30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements.

Integrated bulk and single-cell RNA-sequencing identified disease-relevant monocytes and a gene network module underlying systemic sclerosis.

OBJECTIVE: Immunological disturbances have been reported in systemic sclerosis (SSc). This study assessed the transcriptome disturbances in immune cell subsets in SSc and characterized a disease-related gene network module and immune cell cluster at single cell resolution. METHODS: Twenty-one Japanese SSc patients were enrolled and compared with 13 age- and sex-matched healthy controls (HC). Nineteen peripheral blood immune cell subsets were sorted by flow cytometry and bulk RNA-seq analysis was performed for each. Differential expression and pathway analyses were conducted. Iterative weighted gene correlation network analysis (iWGCNA) of each subset revealed clustered co-expressed gene network modules. Random forest analysis prioritized a disease-related gene module. Single cell RNA-seq analysis of 878 monocytes was integrated with bulk RNA-seq analysis and with a public database for single cell RNA-seq analysis of SSc patients. RESULTS: Inflammatory pathway genes were differentially expressed in widespread immune cell subsets of SSc. An inflammatory gene module from CD16+ monocytes, which included KLF10, PLAUR, JUNB and JUND, showed the greatest discrimination between SSc and HC. One of the clusters of SSc monocytes identified by single-cell RNA-seq analysis characteristically expressed these inflammatory co-expressed genes and was similar to lung infiltrating FCN1hi monocytes expressing IL1B. CONCLUSIONS: Our integrated analysis of bulk and single cell RNA-seq analysis identified an inflammatory gene module and a cluster of monocytes that are relevant to SSc pathophysiology. They could serve as candidate novel therapeutic targets in SSc.

Identifying the most influential gene expression profile in distinguishing ANCA-associated vasculitis from healthy controls.

OBJECTIVE: Previous gene expression analyses seeking genes specific to antineutrophil cytoplasmic antibody-associated vasculitis (AAV) have been limited due to crude cell separation and the use of microarrays. This study aims to identify AAV-specific gene expression profiles in a way that overcomes those limitations. METHODS: Blood samples were collected from 26 AAV patients and 28 healthy controls (HCs). Neutrophils were isolated by negative selection, whereas 19 subsets of peripheral blood mononuclear cells were sorted by fluorescence assisted cell sorting. RNA-sequencing was then conducted for each sample, and iterative weighted gene correlation network analysis (iterativeWGCNA) and random forest were consecutively applied to identify the most influential gene module in distinguishing AAV from HCs. Correlations of the identified module with clinical parameters were evaluated, and the biological role was assessed with hub gene identification and pathway analysis. Particularly, the module's association with neutrophil extracellular trap formation, NETosis, was analyzed. Finally, the module's overlap with GWAS-identified autoimmune disease genes (GADGs) was assessed for validation. RESULTS: A neutrophil module (Neu_M20) was ranked top in the random forest analysis among 255 modules created by iterativeWGCNA. Neu_M20 correlated with disease activity and neutrophil counts but not with the presence of antineutrophil cytoplasmic antibody. The module comprised pro-inflammatory genes, including those related to NETosis, supported by experimental evidence. The genes in the module significantly overlapped GADGs. CONCLUSION: We identified the distinct group of pro-inflammatory genes in neutrophils, which characterize AAV. Further investigations are warranted to confirm our findings as they could serve as novel therapeutic targets.

Associations of Education With Overall Diet Quality Are Explained by Different Food Groups in Middle-aged and Old Japanese Women.

BACKGROUND: The disparity of overall diet quality by personal educational attainment has been a public issue. However, it remains unknown which food groups contribute to the disparity. This cross-sectional study assesses which food groups explain associations between education and overall diet quality in Japanese women. METHODS: A total of 3,788 middle-aged (mean age, 47.7 years) and 2,188 older women (mean age, 74.4 years), who lived in 47 prefectures in Japan, provided data on their education (low, middle, and high) and dietary intakes from a diet history questionnaire. A diet quality score (possible score 0-70) was calculated based on seven food components. Mean diet quality scores, with adjustment for lifestyle and neighborhood variables, were estimated by education using a general linear model, and Dunnett's multiple comparison was conducted. Additionally, mean scores of each food component were estimated by education and compared using the same manner. RESULTS: After adjustment for lifestyle and neighborhood variables, mean diet quality score of high or middle education was higher than low education for both generations. Middle-aged women with high and middle education had higher scores of 'milk', 'snacks, confection, and beverages', 'fruits', and 'vegetable dishes' than those with low education. Older women with high and middle education had higher scores of 'sodium from seasonings' and 'fruits' than those with low education. CONCLUSIONS: This study suggests that positive associations between education and diet quality are explained by different food groups in middle-aged and older Japanese women, which are independent of lifestyle and neighborhood variables.

Working from home and dietary changes during the COVID-19 pandemic: A longitudinal study of health app (CALO mama) users.

It is plausible that the coronavirus disease pandemic and related changes in work and life patterns affected dietary patterns, but existing studies have limitations owing to a cross-sectional design. Using longitudinal data, we examined dietary changes in people due to the pandemic and work and life patterns. We conducted an online survey on changes in work and life patterns during the pandemic from April 30, 2020, to May 8, 2020, among users of a health app called CALO mama provided in Japan. We retrieved and linked the dietary data for 5929 participants from January 1, 2020, to May 13, 2020. Generalized linear mixed models were used to estimate the frequencies of food intake associated with the pandemic and work and life patterns. During the state of emergency, the frequency of intake of vegetables, beans, seaweeds, fish, meats, dairy products, and snacks increased, whereas alcohol intake decreased. Working from home was associated with increased intake of vegetables, fruits, dairy products, and snacks but decreased intake of seaweeds, meats, and alcohol. Time spent on childcare was associated with decreased intake of vegetables and fruits but increased intake of meats. Probable depressive symptoms were negatively associated with the frequency of food intake other than snacks and alcohol. We conclude that diet quality improved during the pandemic in general, but attention must be paid to overconsumption of snacks and negative factors such as increased burden of childcare and depression for healthy eating.

Intake of Coffee Associated With Decreased Depressive Symptoms Among Elderly Japanese Women: A Multi-Center Cross-Sectional Study.

BACKGROUND: Depression in elderly people is a major global concern around the world. Epidemiological evidence of the association of beverages with depressive symptoms has received research attention; however, epidemiological studies on the association of coffee and green tea consumption with depressive symptoms among the elderly population are limited. The objective of this study is to cross-sectionally examine the association of depressive symptoms with the intake of coffee, green tea, and caffeine and to verify the antidepressant effect of caffeine. METHODS: The subjects were 1,992 women aged 65-94 years. Intakes of coffee, green tea, and caffeine, as well as depressive symptoms, were assessed with a validated brief dietary history questionnaire (BDHQ) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Multiple logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for depressive symptoms with adjustments for potential confounders. RESULTS: Coffee intake was associated with a lower prevalence of depressive symptoms, the ORs of which for the 4th versus the 1st quartiles of intake was 0.64 (95% CI, 0.46-0.88, P for trend = 0.01) in a fully adjusted model. Caffeine intake was marginally associated with depressive symptoms, but the association was not statistically significant (OR 0.75; 95% CI, 0.55-1.02, P for trend = 0.058). CONCLUSION: The result suggests that the inverse association of coffee intake with depressive symptoms might be associated with not only caffeine intake but also some other substances in coffee or factors related to coffee intake. Because of the cross-sectional design of the present study, longitudinal studies are required to confirm the present finding.

Relative validity of brief-type self-administered diet history questionnaire among very old Japanese aged 80 years or older.

OBJECTIVE: Dietary questionnaires for assessing dietary intakes among populations of individuals aged 80 years or older (the very old) are very limited. We examined the relative validity of forty-three nutrients and twenty-seven food groups estimated by a brief-type self-administered diet history questionnaire (BDHQ) targeting very old Japanese, using semi-weighed dietary records (DR) as a reference. DESIGN: Between June and August 2012 and between June 2015 and February 2016, a three-day non-consecutive DR (at two-week intervals) and a BDHQ were completed. SETTING: Tokyo, the capital prefecture of Japan. SUBJECTS: Eighty very old Japanese (thirty-six men and forty-four women) aged 82-94 years. RESULTS: The median intakes of 40-70 % of the crude and energy-adjusted nutrients estimated by the BDHQ were significantly different from those estimated by the DR. The median Spearman's correlation coefficient of nutrient intakes between the BDHQ and the DR was 0·39-0·46. About half (48-56 %) of the food groups were significantly different in terms of the median intakes estimated by the BDHQ and the DR in crude and energy-adjusted values. The median Spearman's correlation coefficient between the BDHQ and the DR was 0·45-0·48. CONCLUSIONS: Acceptable Spearman's correlations (≥0·3) were obtained for many dietary intakes among the very old Japanese population. The BDHQ is a good candidate for epidemiological studies among very old Japanese, although, for some nutrients and food groups, the difficulty of estimating accurate median intakes is one of the limitations for the tool. Further efforts to enhance the validity of the BDHQ for very old populations are needed.

Higher dietary glycemic index, but not glycemic load, is associated with a lower prevalence of depressive symptoms in a cross-sectional study of young and middle-aged Japanese women.

OBJECTIVE: Epidemiologic evidence on the associations between dietary glycemic index (GI) and glycemic load (GL) and depressive symptoms is not only limited, particularly in Asian populations where dietary GI and GL are typically higher than in Western countries, but also inconclusive. This cross-sectional study examined these associations in Japanese women. METHODS: Subjects were 3963 young (age 18-years) and 3826 middle-aged (mean age 47.8 years) Japanese women. Dietary GI and GL were assessed using a validated diet history questionnaire. Depression symptoms were defined as present when subjects had a Center for Epidemiologic Studies Depression score ≥16. RESULTS: The prevalence of depressive symptoms was 50.2% for young women and 27.3% for middle-aged women. The mean (SD) values of energy-adjusted dietary GI and GL (GI for glucose = 100) were, respectively, 64.9 (4.3) and 142.0 (27.4) for young women and 65.0 (4.1) and 142.2 (29.5) for middle-aged women. After adjustment for potential confounding factors, higher dietary GI was associated with a lower prevalence of depressive symptoms. Adjusted OR (95% CI) for depressive symptoms in the highest compared to lowest quintiles of dietary GI was 0.66 (0.52, 0.82) for young women (P for trend = 0.001) and 0.75 (0.60, 0.96) for middle-aged women (P for trend = 0.046). Conversely, there was no association between dietary GL and depressive symptoms in either age group. CONCLUSIONS: Dietary GI, but not GL, was inversely associated with depressive symptoms in a group of young and middle-aged Japanese women with relatively high dietary GI and GL.

Higher dietary acid load is associated with a higher prevalence of frailty, particularly slowness/weakness and low physical activity, in elderly Japanese women.

OBJECTIVE: Epidemiologic evidence on the potential effects of dietary acid load on frailty is lacking. This cross-sectional study examined the association between dietary acid load and frailty. METHODS: This study was based on self-reported data obtained from 2176 Japanese women aged 65-94 years. Dietary acid load was characterized as potential renal acid load (PRAL) and net endogenous acid production (NEAP), based on information on nutrient intake, obtained from a validated brief diet history questionnaire. Frailty score (0-5) was defined as the sum of slowness/weakness (two points), exhaustion (one point), low physical activity (one point), and unintentional weight loss (one point). A score of ≥3 was classified as indicating frailty. RESULTS: The prevalence of frailty was 17.9%. After adjustment for potential confounding factors, higher PRAL and NEAP were associated with a higher prevalence of frailty. Adjusted OR (95% CI) for frailty in the highest compared to the lowest quintiles was 1.59 (1.08, 2.34) for PRAL (P for trend = 0.048) and 1.42 (0.98, 2.06) for NEAP (P for trend = 0.03). PRAL and NEAP also showed positive associations with the prevalence of slowness/weakness and low physical activity (all P for trend ≤0.03). PRAL (but not NEAP) was positively associated with the prevalence of exhaustion (P for trend = 0.04). There was no association for unintentional weight loss. CONCLUSIONS: Dietary acid load was positively associated with the prevalence of frailty, particularly slowness/weakness and low physical activity, in elderly Japanese women.

Urine 24-Hour Sodium Excretion Decreased between 1953 and 2014 in Japan, but Estimated Intake Still Exceeds the WHO Recommendation.

Background: Accurate monitoring of sodium intake is necessary for evaluating strategies used to reduce sodium intake. However, no repeat survey has been conducted in representative populations in Japan to examine trends in sodium intake with the use of 24-h urinary sodium excretion, a standard evaluation method for sodium intake monitoring.Objective: The objective of this study was to examine potential trends in sodium intake by examining previous reports of 24-h urinary sodium excretion in healthy Japanese adult populations.Methods: We systematically searched for reports of 24-h urinary sodium excretion in healthy Japanese adult populations (mean age range: 18-69 y). We searched PubMed and Web of Science for English-language articles and hand-searched 7 Japanese scientific journals for Japanese-language articles. Trends in urinary sodium excretion were examined with the use of weighted linear regression and random-effects meta-regression analyses, with adjustment or stratification to address study characteristics (population mean age, percentage of men, and sample size) and study assessment for completeness of urine collection.Results: We identified 68 reports of urinary sodium excretion from 53 articles published from 1953 through 2014 that showed high rates of urinary sodium excretion in healthy Japanese adult populations (weighted mean: 4900 mg/d). The rate of urinary sodium excretion significantly decreased between 1953 and 2014, by 4350 mg/d (P < 0.001); however, the rate of reduction in urinary sodium excretion was variable and decreased with time (P-linear trend <0.001 and P-quadratic trend <0.001). In the random-effects meta-regression analysis of studies that assessed completeness of urine collection with creatinine excretion, no significant relation between urinary sodium excretion and year was observed from 1978 to 2014 (ß = -16, P = 0.40).Conclusion: Despite a decrease in urinary sodium excretion in healthy Japanese adult populations between 1953 and 2014, sodium intake still exceeds the WHO recommendation for adults. This review was registered at PROSPERO as CRD42016035452.

Food-based diet quality score in relation to depressive symptoms in young and middle-aged Japanese women.

Only a few studies have focused on the association between overall diet, rather than intakes of individual nutrients or foods, and depressive symptoms in Japanese. This cross-sectional study examined associations between a diet quality score and depressive symptoms in 3963 young (age 18 years) and 3833 middle-aged (mean age 47·9 (sd 4·2) years) Japanese women. Dietary information was collected using a diet history questionnaire. A previously developed diet quality score was computed mainly based on the Japanese Food Guide Spinning Top. The prevalence of depressive symptoms was 22·0 % for young women and 16·8 % for middle-aged women, assessed as a Center for Epidemiologic Studies Depression (CES-D) score ≥23 and ≥19, respectively. As expected, the diet quality score was associated positively with intakes of 'grain dishes', 'vegetable dishes', 'fish and meat dishes', 'milk' and 'fruits' and inversely with intakes of energy from 'snacks, confection and beverages' and Na from seasonings. After adjustment for potential confounders, OR for depressive symptoms in the highest v. lowest quintiles of the diet quality score was 0·65 (95 % CI 0·50, 0·84) in young women (P for trend=0·0005). In middle-aged women, the corresponding value was 0·59 (95 % CI 0·45, 0·78) (P for trend<0·0001). Analyses where the diet quality and CES-D scores were treated as continuous variables also showed inverse associations. In conclusion, this cross-sectional study showed that a higher diet quality score was associated with a lower prevalence of depressive symptoms in young and middle-aged Japanese women. Prospective studies are needed to confirm a public health relevance of this finding.

Living status and frequency of eating out-of-home foods in relation to nutritional adequacy in 4,017 Japanese female dietetic students aged 18-20 years: A multicenter cross-sectional study.

BACKGROUND: Living status (e.g., living with family or alone) may affect dietary habits. We compared nutritional adequacy according to living status and the frequency of eating out-of-home foods in young Japanese women. METHODS: Female dietetic students (aged 18-20 years; n = 4,017) participated in a cross-sectional multicenter study, which was conducted in 85 dietetic schools in 35 of 47 prefectures in Japan. Habitual dietary intake was assessed with a validated diet history questionnaire. Nutritional adequacy was determined based on the Dietary Reference Intakes for Japanese, 2015, for two goals: preventing non-communicable chronic disease (a tentative dietary goal for preventing lifestyle-related diseases [DG] that tracks five nutrients) and avoiding insufficient intake of mainly vitamins and minerals (estimated average requirement [EAR] that tracks 14 nutrients). RESULTS: Women living with their family were less likely to meet DG nutrient levels, but more likely to meet EAR nutrient levels compared with those living alone. In contrast, women living alone had more inadequate nutrients with EAR and fewer nutrients with not-meeting DG than those living with families. A higher frequency of eating out-of-home was significantly associated with a higher prevalence of not-meeting DG nutrient levels only in the women living with their family. CONCLUSIONS: The prevalence of nutritional adequacy varied based on living status. In addition, women living with their family and those with a high frequency of eating out-of-home foods had the highest prevalence of not-meeting DG. Effective ways of improving dietary quality among young Japanese women differ by living status.

Diet with a combination of high protein and high total antioxidant capacity is strongly associated with low prevalence of frailty among old Japanese women: a multicenter cross-sectional study.

BACKGROUND: The intake of protein and antioxidants has been inversely associated with frailty, individually. However, to our knowledge, no study has evaluated these associations in considering antioxidants or protein intakes as respective confounders. Further, the cooperative effect of dietary protein and antioxidants on frailty has not been investigated. Therefore, we examined the association of high protein and high dietary total antioxidant capacity (TAC) with frailty under the adjustment for dietary TAC or protein intake, respectively. The association between the combination of high dietary protein and high dietary TAC and frailty was also investigated. METHODS: A total of 2108 grandmothers or acquaintances of dietetic students aged 65 years and older participated in this cross-sectional multicenter study conducted in 85 dietetic schools in Japan. Dietary variables, including protein intake, and dietary TAC were estimated from a validated brief-type self-administered diet history questionnaire. Frailty was defined as a score of three or more points obtained from the following four components: slowness and weakness (two points), exhaustion, low physical activity, and unintentional weight loss. RESULTS: Median (interquartile range) age of the present subjects was 74 (71-78) years. Multivariate adjusted ORs (95% CIs) for frailty in the highest compared to the lowest tertile were 0.66 (0.49, 0.87) for total protein intake (P for trend = 0.003) and 0.51 (0.37, 0.69) for dietary TAC (P for trend <0.0001) after adjustment for dietary TAC or total protein intake, respectively. The OR of frailty for the group with both the highest tertiles of total protein intake and dietary TAC was markedly lower (multivariate adjusted OR [95% CIs]: 0.27 [0.16, 0.44]; P <0.0001) compared to the group with the lowest tertile of protein intake and the lowest tertile of dietary TAC. CONCLUSIONS: Both protein intake and dietary TAC were independently inversely associated with frailty among old Japanese women. Further, a diet with the combination of high dietary protein and high dietary TAC was strongly inversely associated with the prevalence of frailty in this population. To select food combinations that allow for an increase of both protein and antioxidants in diet according to the local food culture and dietary habits may be an effective strategy for frailty prevention.

A Japanese diet with low glycaemic index and glycaemic load is associated with both favourable and unfavourable aspects of dietary intake patterns in three generations of women.

OBJECTIVE: Western studies have suggested cultural differences in food and nutrient intake patterns associated with dietary glycaemic index (GI) and glycaemic load (GL). Here, we conducted a cross-sectional study to examine the GI and GL of Japanese diets in relation to food and nutrient intakes. DESIGN: Dietary intake was assessed using a validated, self-administered, diet history questionnaire. SETTING: A total of thirty-five of forty-seven prefectures in Japan. SUBJECTS: Young (age 18 years), middle-aged (mean age 48 years) and older (mean age 74 years) Japanese women (n 3961, 3800 and 2202, respectively). RESULTS: Irrespective of age, a positive association with dietary GI was seen for white rice only, which contributed most (37-42 %) to the variation in dietary GI. Conversely, all other food groups (such as fruit and vegetable juice, dairy products, noodles and fruit) were negative predictors of dietary GI. For dietary GL, 95-96 % of variation was explained by carbohydrate-rich food groups, all of which were positive predictors of GL. After adjustment for potential confounding factors, only carbohydrate intake was positively associated with dietary GI and GL, irrespective of age. Conversely, dietary GI and GL were inversely associated with intakes of all other nutrients examined (including SFA and Na). CONCLUSIONS: A low-GI and -GL diet, which was characterized principally by a low intake of white rice, was associated with both favourable (higher intakes of dietary fibre and key vitamins and minerals) and unfavourable (higher intakes of SFA and Na) aspects of dietary intake patterns in three generations of Japanese women.