Kazunori Ikebe

Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B

UNLABELLED Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis. OBJECTIVE We assessed the hypothesis that 9p21 locus polymorphisms influence the expression of the transcripts in the region (ANRIL, CDKN2A/B) and that these transcripts contribute to atherogenesis through the modulation of proliferation in VSMC. METHODS We genotyped 18 SNPs (r(2)<0.8 and MAF>0.05) across the region of interest: CDKN2A/B and ANRIL, encompassing the CVD-associated region. RNA and DNA were extracted from the blood of 57 volunteers (69-72 years old). Carotid ultrasound was performed in 56 subjects. CDKN2A/B and ANRIL (exons 1-2 and 17-18) expression was measured employing RT-PCR. Gene expression and cell growth were evaluated in cultured VSMC after the siRNA-mediated knock-down of ANRIL. RESULTS The risk alleles for atherosclerosis-related phenotypes were consistently associated with a lower expression of ANRIL when evaluating exons 1-2. Common carotid artery stenosis was associated with a significantly lower (P<0.01) expression of ANRIL (exons 1-2). ANRIL knock-down in VSMC caused significant variation in expression of CDKN2A/B (P<0.05) and reduction of cell growth (P<0.05) in vitro. CONCLUSION Disease-associated SNPs at the 9p21 locus predominantly affect the expression of ANRIL. Overall, our results suggest that several CVD-associated SNPs in the 9p21 locus affect the expression of ANRIL, which, in turn modulate cell growth, possibly via CDKN2A/B regulation.

Association of masticatory performance with age, gender, number of teeth, occlusal force and salivary flow in Japanese older adults: Is ageing a risk factor for masticatory dysfunction?

OBJECTIVE In general, ageing is a risk factor for sensory and motor deterioration, with the rate of decline varying amongst individuals. Concerning masticatory function, missing teeth along with oral disease seem to accelerate the dysfunction. Here, we aimed to confirm whether masticatory dysfunction by ageing is inevitable. This study investigated the effect of age, gender, number of natural teeth, occlusal force and salivary flow on the masticatory performance in a large sample of elderly adults. DESIGN The study sample consisted of 1288 independently living people aged 60-84 years. Masticatory performance was determined by the comminuted particles of test food. Bilateral maximal occlusal force in the intercuspal position was measured with pressure sensitive sheets. Stimulated whole saliva was collected. RESULTS Masticatory performance was significantly correlated to age, number of residual teeth, occlusal force and stimulated salivary flow rate by Pearsons correlation test. The multiple linear regression analysis showed that, with other variables controlled, masticatory performance was significantly associated with the number of residual teeth (β=0.456, P<0.001), occlusal force (β=0.244, P<0.001) and stimulated salivary flow rate (β=0.069, P=0.003). Age was not related to masticatory performance (β=-0.007, P=0.753). CONCLUSIONS Declines in the number of residual teeth, occlusal force and salivary flow were associated with a reduction of masticatory performance in older adults. If tooth loss is not considered as an attribute of physiological ageing, then ageing by itself may not be a risk factor for masticatory dysfunction.

Effectiveness and fabrication of mouthguards.

Although mouthguards have been suggested as a means for preventing dental traumatic injuries, there are still some controversies over some aspects such as effectiveness in preventing concussions, material selections, method for fabrication, design, side effects and so on. The purpose of this literature review was to clarify differences in opinions with supporting evidence on these issues and find the best guidelines for promoting usage and providing mouthguards with better protective capability and fewer side effects such as difficulty in breathing and speaking.

Masticatory performance in older subjects with varying degrees of tooth loss.

OBJECTIVES The purpose of this study was to establish the factors influencing the masticatory performance of older subjects with varying degrees of tooth loss and associated numbers of posterior occlusal contacts. METHODS The subjects consisted of 1274 independently living people aged 60 years and over. Individuals with partially or fully edentulous arches without a denture replacement or those having any symptoms related to an oral problem were excluded from the study participants. Masticatory performance, maximal occlusal force and stimulated whole saliva were measured. Subjects were grouped into three categories by posterior occlusal contact, according to the Eichner Index. Group A had contacts in four support zones; group B had one to three zones of contact or contact in the anterior region only; and group C had no support zones at all, although a few teeth could still remain. RESULTS The masticatory performance in groups B and C was found to be 81% and 50% of that of group A, respectively. The multiple linear regression analysis showed that in all the groups, occlusal force was significantly associated with masticatory performance. In groups A and B, the number of residual teeth was significantly associated with masticatory performance, whereas in group C, it had no significant relationship with masticatory performance. Salivary flow rate had a significant correlation with masticatory performance only in group C. CONCLUSIONS Declines in occlusal contact, occlusal force and salivary flow appear to be associated with reduction of masticatory performance in older adults. However, the crucial factors for masticatory performance varied, depending on the phase of occlusal collapse.

Patterns of missing occlusal units and oral health-related quality of life in SDA patients

The aim of this study was to explore the relationship between patterns of missing occlusal units (OUs) and oral health-related quality of life (OHRQoL) in subjects with the shortened dental arches (SDAs). Subjects with SDAs were recruited consecutively for 1 month from six university-based prosthodontic clinics. In total, 115 SDA subjects participated (mean age, 58.5 +/- 10.0 years; 71% female). The location and number of missing teeth were examined and the number of missing OUs was calculated. To evaluate OHRQoL, the Japanese version of the Oral Health Impact Profile (OHIP-J) was administered and the summary score of OHIP-J was calculated. The SDA subjects were categorized depending upon the anterior-posterior lengths of the missing or remaining OUs. Regression analyses were performed to investigate the OHIP-J differences between groups of subjects with various anterior-posterior SDA lengths. The analyses revealed that subjects who only lost the second molar contact exhibited significantly better OHRQoL than those who lost more teeth [coefficient: 11.1, 95% confidence interval (CI): 2.8-19.2, P = 0.02]. Furthermore a statistically significant group difference was observed between the groups with and without the first molar occlusal contact (coefficient: 12.8, 95% CI: 1.4 to 24.1, P = 0.03). In conclusion, although our results are of exploratory nature and need validation, patterns of missing OUs are likely to be related to the OHRQoL impairment in SDA subjects with the presence of first molar contact having a particularly important role.

Cysteine proteinase from Streptococcus pyogenes enables evasion of innate immunity via degradation of complement factors.

Background: Patients with C1-INH deficiency and streptococcal toxic shock syndrome show similar symptoms. Results: A streptococcal cysteine protease degrades complement factors and protects bacteria against complement system bactericidal effects. Conclusion: Streptococcus pyogenes evades complement system eradication by its own cysteine protease. Significance: Our findings clarify the mechanism shown in previous clinical case reports and are important for future applications. Streptococcus pyogenes is an important human pathogen that causes invasive diseases such as necrotizing fasciitis, sepsis, and streptococcal toxic shock syndrome. We investigated the function of a major cysteine protease from S. pyogenes that affects the amount of C1-esterase inhibitor (C1-INH) and other complement factors and aimed to elucidate the mechanism involved in occurrence of streptococcal toxic shock syndrome from the aspect of the complement system. First, we revealed that culture supernatant of a given S. pyogenes strain and recombinant SpeB degraded the C1-INH. Then, we determined the N-terminal sequence of the C1-INH fragment degraded by recombinant SpeB. Interestingly, the region containing one of the identified cleavage sites is not present in patients with C1-INH deficiency. Scanning electron microscopy of the speB mutant incubated in human serum showed the abnormal superficial architecture and irregular oval structure. Furthermore, unlike the wild-type strain, that mutant strain showed lower survival capacity than normal as compared with heat-inactivated serum, whereas it had a significantly higher survival rate in serum without the C1-INH than in normal serum. Also, SpeB degraded multiple complement factors and the membrane attack complex. Flow cytometric analyses revealed deposition of C9, one of the components of membrane the attack complex, in greater amounts on the surface of the speB mutant, whereas lower amounts of C9 were bound to the wild-type strain surface. These results suggest that SpeB can interrupt the human complement system via degrading the C1-INH, thus enabling S. pyogenes to evade eradication in a hostile environment.

Comparison of GOHAI and OHIP‐14 measures in relation to objective values of oral function in elderly Japanese

OBJECTIVES The aims of this study were to assess the correlations between the Geriatric Oral Health Assessment Index (GOHAI) and the Oral Health Impact Profile-14 (OHIP-14) and to examine which survey is more sensitive to objectively measured oral function in the Japanese elderly. METHODS The subjects were 290 community-dwelling, cognitively healthy, and independently living people over the age of 60 years (mean: 66.3 years). Measures included the GOHAI and OHIP-14 questionnaires, as well as self-rating of general and oral health, dry mouth, number of residual teeth, and objective values of occlusal force, masticatory performance, and salivary flow rate. Bivariate and linear regression analyses were used to identify which of these variables predicted GOHAI and OHIP-14 scores. RESULTS Spearmans correlation coefficient between the GOHAI and OHIP-14 scores was 0.728 (P < 0.001), although the OHIP-14 showed a greater number of 0 scores, suggesting a greater floor effect. At the bivariate level, self-rating of general and oral health, dry mouth, number of residual teeth, occlusal force, and masticatory performance were associated with GOHAI and OHIP-14 scores. Multiple linear regression analyses showed that after controlling for the other significant variables, both the occlusal force (standardized regression coefficient [β] = -0.164, P = 0.004) and masticatory performance (β = -0.125, P = 0.019) had significant associations with the GOHAI score, whereas this association was not found with the OHIP score. CONCLUSIONS Although the GOHAI and OHIP-14 had a strong correlation, the GOHAI was more sensitive to the objective values of oral functions among independently living elderly persons in Japan.

Effect of Reinforcement on Overdenture Strain

Because the abutment becomes the fulcrum, and the denture base over the coping is usually thin, the overdenture is susceptible to fracture. We hypothesized that rational reinforcement can reduce strain and prevent deformation and fracture of the overdenture. We investigated the effect of reinforcement on overdenture strain around the copings and at a midline. A mandibular edentulous model with a 2-mm-thick artificial mucosa and abutment teeth installed bilaterally in the canine position was produced. The coping had a dome-shaped upper surface with a height of 6 mm. On the lingual polished surface, strain gauges were attached at the canine position and at the midline. A vertical load of 49 N was applied on the occlusal surface. Among several kinds of reinforcements, the cast metal reinforcement that covers both the midline and the coping top significantly reduced the strain on the overdenture. It is suggested that this simple reinforcement is effective in preventing deformation and fracture of the overdenture.

Significance of occlusal force for dietary fibre and vitamin intakes in independently living 70-year-old Japanese: from SONIC Study

OBJECTIVES The number of teeth has frequently been used as an indicator of oral health in investigations of food intake; however, this measure does not represent the efficacy of the masticatory performance. Masticatory performance may be more important for food selection and avoidance than number of remaining teeth. The aim of this study was to investigate the association of occlusal force with habitual dietary intakes in independently living older Japanese. METHODS The study population was 757 community-dwelling people aged 69-71 years old. Bilateral maximal occlusal force in the intercuspal position was measured with pressure-sensitive sheets. Removable denture wearers kept their dentures in place during the measurements. Dietary habits during the preceding month were assessed using a brief-type self-administered diet history questionnaire that measures consumption frequencies of selected food commonly consumed and calculates energy-adjusted dietary intakes. Linear trends of food and nutrient intakes with decreasing occlusal force were tested after adjusting for gender and socioeconomic factors. RESULTS After adjusting for socioeconomic status and the number of remaining teeth, decline of occlusal force was significantly associated with lower intakes of vegetables, vitamins A, C, B6, folate, and dietary fibre (P for trend<0.05). In contrast, number of teeth was significantly associated only with calcium and zinc, controlling for occlusal force. CONCLUSIONS It is concluded that occlusal force was significantly associated with intakes of vitamins and dietary fibre rather than number of remaining teeth in independently living older Japanese.

Age and sex differences in the taste sensitivity of young adult, young-old and old-old Japanese

The present study examined sex and age differences in taste sensitivity among young adult, young‐old and old‐old Japanese.