Low Body Mass Index as a Risk Factor for the Onset of Porosity of the Mandibular Bone in the Elderly

Objective: To investigate whether a low body mass index (BMI) has a significant relationship with mandibular bone porosity progression by conducting a mandibular inferior cortex (MIC) classification in elderly Japanese people. Material and Methods: A total of 266 study subjects, aged 70 at baseline, were recruited for this study, conducted from 1998 to 2007. The subjects were divided into two groups according to changes in the MIC on serial panoramic radiographs during this nine-year study period: a no change group (MIC-NC) and a change group (MIC-C). All subjects in the MIC-C showed changes trending toward greater fragility. We evaluated the BMI at baseline. Logistic regression analysis was performed to assess the relationship between the MIC condition during the nine-year period (0: MIC-NC, 1: MIC-C) and BMI (kg/m2) adjusted for gender, current health status (CHS), and smoking habit (SH) at baseline. Results: The mean and standard deviations of the BMI at baseline in the MIC-NC and MIC-C were 22.8 ± 2.1 and 21.8 ± 2.5 kg/m2 for males and 23.1 ± 2.9 and 21.9 ± 2.4 kg/m2 for females. There was a significant relationship between the MIC condition and the BMI in both males (p=0.04) and females (p=0.01). The logistic regression analysis revealed a significant association between the MIC condition over the nine-year period and the BMI (OR=0.84, p=0.003), which was adjusted depending on the gender (OR=5.18, p=0.000), CHS (OR=0.53, p=0.015), and SH (OR=4.15, p=0.002) at baseline. Conclusion: A low BMI carries a risk of developing mandibular bone porosity by measuring the MIC condition in panoramic radiographs

Oral health status: relationship to nutrient and food intake among 80‐year‐old Japanese adults

Objectives The aim of this cross‐sectional study was to investigate the relationship of oral health status defined on the basis of presence of posterior occluding pairs ( POP s) and adequacy of removable denture fit as determined by self‐report to nutrient and food intake among older Japanese. Methods The subjects were 353 Japanese aged 80 years in 2008 and were classified into four groups according to the number of POP s, defined as pairs of occluding natural, restored, or fixed prosthetic postcanine teeth (range: 0–8) and removable denture status. The groups were: (i) good dentition ( n  =   56; 8 POP s and no removable prosthesis), (ii) well‐fitting dentures ( n  =   158; <8 POP s with self‐reported good‐fitting dentures), (iii) ill‐fitting dentures ( n  =   70; <8 POP s with self‐reported ill‐fitting dentures), and (iv) compromised dentition ( n  =   69; <8 POP s and no removable prosthesis). Multivariable analysis of the differences in nutrient and food intake outcome variables which were collected via validated food frequency questionnaire among the four oral health status groups was conducted using general linear models. Results Intake of multiple nutrients was significantly ( P  <   0.05) lower in the group with ill‐fitting dentures or compromised dentition than in the good dentition group. Vegetable, fish, and shellfish consumption was significantly lower in the ill‐fitting dentures or compromised dentition groups. No significant differences were seen in dietary intake between the well‐fitting dentures and good dentition groups. Conclusions Dietary intake was poorer in those with self‐perceived ill‐fitting dentures or fewer POP s than among those having all POP s. Regular dental care to maintain intact dentition, as well as dental treatment to replace missing teeth and ensure adequate denture fit and function, may be important to the diet intake and subsequent nutritional status of older Japanese.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108691/1/cdoe12100.pd

Effect of lifestyle on 6‐year periodontitis incidence or progression and tooth loss in older adults

AimTo evaluate the longitudinal association of combined healthy lifestyle factors with incidence or progression of periodontitis and tooth loss in older adults.Materials and methodsThis 6‐year study included 374 Japanese 70‐year olds with 7,157 teeth, from a source eligible baseline population of 554 individuals. Four lifestyle factors—cigarette smoking, physical activity, relative weight, and dietary quality—were scored as healthy (1 point) or unhealthy (0 point). Adding the individual scores generated the “healthy lifestyle score” (0–4 points). Multilevel mixed‐effects logistic regression models were applied to evaluate tooth‐specific associations between the baseline healthy lifestyle score and the incidence or progression of periodontitis (increase in clinical attachment loss ≥3 mm) and tooth loss.ResultsAfter 6 years, 19.0% of the teeth exhibited periodontitis incidence or progression and 8.2% were lost. Compared with a healthy lifestyle score of 0–1 (least healthy), the highest score (4 points) was associated with a significantly lower tooth‐specific risk of periodontitis (adjusted odds ratio = 0.32; 95% confidence interval: 0.16–0.62) and tooth loss (adjusted odds ratio = 0.42; 95% confidence interval: 0.23–0.77).ConclusionsSimultaneous adherence to multiple healthy lifestyle factors significantly lowers the risk of incidence or progression of periodontitis and tooth loss in older adults.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145573/1/jcpe12920_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145573/2/jcpe12920.pd

Association of liver enzyme levels and alveolar bone loss : a cross-sectional clinical study in Sado Island

The interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults. Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis. After adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable. There was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults

Promotion of IL-4- and IL-5-dependent differentiation of anti-μ-primed B cells by ascorbic acid 2-glucoside

The stable ascorbic acid derivative 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) was used to investigate the role of ascorbic acid (AA) in B cell differentiation in vitro. AA-2G is stable in a solution unlike AA but is hydrolyzed by cellular alpha-glucosidase to release AA. Mouse spleen B cells were primed for 2 days with an anti-mu antibody in the presence of interleukin (IL)-4 and IL-5 and then washed and recultured with AA-2G in the presence of IL-4 and IL-5. AA-2G, but not AA, dose-dependently increased IgM production, the greatest enhancement being 150% at concentrations of more than 0.5 mM. In the absence of IL-4 and IL-5, primed B cells produced a negligible amount of IgM, and AA-2G had no effect. AA-2G-induced IgM production in the presence of IL-4 and IL-5 was inhibited by the alpha-glucosidase inhibitor castanospermine. Intracellular AA content, depleted during the priming period, increased by adding AA-2G at the start of reculture. Treatment of B cells with AA-2G resulted in an increase in the number of IgM-secreting cells, CD138-positive cells and CD45R/B220-negative cells. The number of viable cells in untreated cultures decreased gradually, but the decrease was significantly attenuated by AA-2G, resulting in about 70% more viable cells in AA-2G-treated cultures. AA-2G caused a slight but reproducible enhancement of DNA synthesis and a slight decrease in the number of cells with a sub-G1 DNA content. These results demonstrated that AA released from AA-2G enhanced cytokine-dependent IgM production in anti-mu-primed B cells and suggest that its effect is caused through promoting the differentiation of B cells to plasma cells and attenuating the gradual decrease in the number of viable cells

Hyposalivation and 10‐year all‐cause mortality in an elderly Japanese population

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143602/1/ger12319.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143602/2/ger12319_am.pd

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target