Oral Health and Nutritional Intake in Community-Dwelling 90-Year-Old Japanese People: A Cross-Sectional Study.

INTRODUCTION: This study aimed to determine the relationship between dentition, mastication, salivation and nutritional intake in 90-year-old Japanese people. METHODS: This cross-sectional study included 84 participants (39 men and 45 women) aged 90 years. We used questionnaires to collect demographic information, smoking status, nutritional intake and higher-level functional capacity. Nutritional intake was assessed using the validated Brief-Type Self-Administered Diet History Questionnaire, and higher-level functional capacity was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) questionnaire. Oral examinations, masticatory performance tests, stimulated salivary flow rate (SSF) tests, blood tests, blood pressure tests and body mass index (BMI) assessments were conducted. Univariable and multivariable linear regression analyses were performed. RESULTS: Multivariable linear regression analyses adjusted for sex, education, TMIG-IC and BMI ≤20 kg/m2 showed that participants with masticatory performance <173 mg/dL had lower intake of folic acid and vitamin A than those with masticatory performance ≥173 mg/dL. SSF was positively associated with intake of vitamin A. The number of teeth was positively associated with the intake of ß-carotene. With smaller effect sizes, masticatory performance, SSF and number of teeth were also associated with the intake of various micronutrients and carbohydrates. CONCLUSION: Lower masticatory performance, lower SSF and fewer teeth were associated with a lower intake of several micronutrients, such as vitamin A, ß-carotene and folic acids, in Japanese individuals of advanced age. Oral health practitioners should pay careful attention to the nutritional intake of older people with poor mastication, dry mouth and severe tooth loss.

Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout.

The ABCG2 gene is a well-established hyperuricemia/gout risk locus encoding a urate transporter that plays a crucial role in renal and intestinal urate excretion. Hitherto, p.Q141K-a common variant of ABCG2 exhibiting approximately one half the cellular function compared to the wild-type-has been reportedly associated with early-onset gout in some populations. However, compared with adult-onset gout, little clinical information is available regarding the association of other uricemia-associated genetic variations with early-onset gout; the latent involvement of ABCG2 in the development of this disease requires further evidence. We describe a representative case of familial pediatric-onset hyperuricemia and early-onset gout associated with a dysfunctional ABCG2, i.e., a clinical history of three generations of one Czech family with biochemical and molecular genetic findings. Hyperuricemia was defined as serum uric acid (SUA) concentrations 420 µmol/L for men or 360 µmol/L for women and children under 15 years on two measurements, performed at least four weeks apart. The proband was a 12-year-old girl of Roma ethnicity, whose SUA concentrations were 397-405 µmol/L. Sequencing analyses focusing on the coding region of ABCG2 identified two rare mutations-c.393G>T (p.M131I) and c.706C>T (p.R236X). Segregation analysis revealed a plausible link between these mutations and hyperuricemia and the gout phenotype in family relatives. Functional studies revealed that p.M131I and p.R236X were functionally deficient and null, respectively. Our findings illustrate why genetic factors affecting ABCG2 function should be routinely considered in clinical practice as part of a hyperuricemia/gout diagnosis, especially in pediatric-onset patients with a strong family history.

Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients.

OBJECTIVES: Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000-3000 years. METHODS: Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype. RESULTS: In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10-8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients' gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout. CONCLUSIONS: Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.

Contraction stresses in direct and indirect composite restorations compared by crack analysis.

PURPOSE: To compare contraction stresses in direct and indirect composite restorations using crack analysis. MATERIALS AND METHODS: Glass disks with a central cylindrical hole were prepared. Initial cracks were made in the glass using a Vickers indenter at various distances from the edge of the hole. The indentation crack lengths were measured parallel to the tangent of the edge of the hole. Silanized holes were directly or indirectly filled with a resin composite. The composite was either self-curing and light curing or only self-curing. Various thicknesses of composite cement were applied to the indirect restorations. The crack lengths were re-measured 15 and 30 min after they were filled. The contraction stresses were calculated from the crack lengths and fracture toughness of the glass. Elastic moduli of light-cured and self-cured composite samples were measured using a nanoindentation method 15 and 30 min after curing. RESULTS: The stress could not be calculated for the light-cured direct composite and light-cured indirect composite restorations with thicker cement, due to glass failure caused by the contraction stress. Glass failure did not occur in the indirect composite restoration with thinner cement or in the self-cured direct composite restoration. The stress in the glass was lower for greater distances or shorter times. Factors of indentation-hole distance and restorative procedure significantly affected the stress. The measuring time and the type of curing had significant influence on the elastic modulus. CONCLUSION: Light-cured indirect composite restorations with a cement thickness < 200 µm generated less contraction stress than did light-cured direct composite restorations. The lowest contraction stress was developed in the self-cured direct composite restoration.

Identification of an exporter that regulates vitamin C supply from blood to the brain.

Vitamin C (VC) distribution in our body requires VC transporters. However, mammalian VC exporters are yet to be identified. Herein, to unravel this long-standing mystery, we focused on the pathways whereby VC moves from blood to the brain, which should require a VC entrance and exit system composed of an importer and a latent exporter. Via cell-based transport analyses of VC efflux and using knockout mice generated via the CRISPR-Cas9 system, we identified GLUT12/SLC2A12 as a physiologically important VC efflux protein expressed in the choroid plexus; Glut12/Slc2a12 knockout halved the cerebral VC levels, markedly increased VC accumulation in the choroid plexus, and reduced the cerebrospinal fluid VC levels. These findings facilitate our understanding of VC regulation and the physiological impact of VC in our body.

Underweight and early childhood caries among young children in rural Cambodia: a pilot study.

OBJECTIVES: To investigate the association between underweight and early childhood caries (ECC) among children aged one to three years in rural Cambodia. MATERIALS AND METHODS: A total of 200 Cambodian children aged one to three years at several villages in Kampong Cham province participated in this study. The children whose Z scores were below two and three standard deviations were considered as moderately-underweight and severely-underweight. Children whose mid-upper arm circumstance (MUAC) was below 12.5 cm, were regarded as having malnutrition. ECC was recorded following the WHO guidelines. Associated factors were obtained through interviews with caregivers. RESULTS: 33.5% and 7.0% of the children were identified as being moderately-underweight and severely-underweight, respectively. The prevalence of ECC was 61.5%. ECC was significantly associated with children being moderately-underweight (P < 0.05). The prevalence of ECC was higher prevalence of those who with severely-underweight, although significant differences were not observed (P = 0.054). Logistic regressions showed that those with low birth weight (OR = 2.57; 95% CI = 1.03-6.40) and malnutrition (OR = 4.71; 95% CI = 1.08-20.62) were likely to be moderately-underweight and severely-underweight, whereas those who with ECC had more moderately-underweight, although it was not significant (OR = 2.21; 95% CI = 0.97-5.00). Those with low birth weight (OR = 10.68; 95% CI = 2.95-38.65) and ECC (OR = 6.67; 95% CI = 1.02-43.61) were likely to be severely-underweight. CONCLUSION: The findings of this study suggest that low birth weight, malnutrition and ECC were associated factors of underweight in this population.

Association between Early Childhood Caries and Maternal Factors among 18- to 36-month-old Children in a Rural Area of Cambodia.

PURPOSE: To investigate the associations between early childhood caries (ECC) and maternal factors among 18- to 36-month-old children in one rural province of Cambodia. MATERIALS AND METHODS: 121 mother-child pairs (male = 67, female = 54; mean age = 25.18 ± 6.24 months) were recruited at several villages in Stueng Trang district, Kampong Cham province. ECC and maternal caries experience were recorded following WHO guidelines. Maternal factors such as literacy and socioeconomic status, as well as child-rearing behaviours, were assessed through an interview questionnaire of the mothers. RESULTS: ECC and maternal caries prevalence were 54.5% and 84.3%, respectively. Statistically significant associations were found between ECC and: breast-feeding after 18 months; sugary food and beverage intake for the child (p < 0.05); maternal caries experience; illiteracy; night-time breastfeeding, bottle feeding, and late introduction of toothbrushing for the child (p < 0.01). A logistic regression revealed that ECC was more common in children whose mothers had DMFT > 0 (OR = 4.08; 95% CI =1.13-14.75; p = 0.032), children whose mothers were illiterate (OR = 8.21; 95% CI = 1.67-40.85; p = 0.009), children who had night-time breastfeeding after 18 months (OR = 2.76; 95% CI = 1.06-7.19; p = 0.037), and children for whom toothbrushing was introduced after 18 months (OR = 2.87; 95% CI = 1.03-7.97; p = 0.042). CONCLUSION: The findings of this study suggest that maternal caries experience and illiteracy, as well as a range of child-rearing behaviours including prolonged night-time breastfeeding and late introduction of toothbrushing were indicators for ECC in this population.

Polymerization stresses in low-shrinkage dental resin composites measured by crack analysis.

OBJECTIVE: The objective of this study was to compare several dental restoratives currently advertised as low-shrinkage composites (Clearfil Majesty Posterior, Kalore, Reflexions XLS Dentin and Venus Diamond) with a microfill composite (Heliomolar) in terms of polymerization stress, polymerization shrinkage and elastic modulus. METHODS: Cracks were made at several distances from the edge of a precision cavity in a soda-lime glass disk. The composites were placed into the cavity and lengths of the cracks were measured before and after light curing. Polymerization stresses generated in the glass at 2 and 10 min after the irradiation were calculated from the crack lengths and K(c) of the glass. Polymerization shrinkage and elastic modulus of the composites also were measured at 2 and 10 min after irradiation using a video-imaging device and a nanoindenter, respectively. The data were statistically analyzed by ANOVAs and Tukey's test (p<0.05). RESULTS: The stress was significantly affected by composite brand, distance and time. The stress was directly proportional to time and inversely proportional to distance from the edge of the cavity. Clearfil Majesty Posterior demonstrated the highest stress and it resulted in the fracture of the glass at 2 min. Venus Diamond and Heliomolar exhibited the greatest shrinkage at both times. The elastic moduli of Clearfil Majesty Posterior and Reflexions XLS Dentin were greatest at 2 and 10 min, respectively. SIGNIFICANCE: Among the four low-shrinkage composites, two demonstrated significantly reduced polymerization stress compared to Heliomolar, which has previously been shown in in vitro tests to generate low curing stress.

Orosensory deprivation alters taste-elicited c-Fos expression in the parabrachial nucleus of neonatal rats.

In the present study we examined the effects of neonatal orosensory deprivation on taste-elicited gustatory activity in the rat parabrachial nucleus (PBN) using the functional anatomical marker c-Fos. Animals in three groups (GG, GO and GM) received gastric cannula implantation surgery on postnatal day 9 (P9). Animals in the fourth group (MR) did not receive any surgery. GG rats were fed by infusion of artificial milk directly into the stomach. GO rats were fed by intraoral infusion of artificial milk. GM and MR rats were reared by their mother with free access to mother's milk, water and rat chow. Rats from all groups were similar in body weight and length by P21. On P21 rats in all groups were intraorally presented with 0.5M sucrose solution and the brains were extracted and processed for c-Fos immunohistochemistry. Taste-elicited c-Fos expression in both the gustatory waist area, and the external lateral subnucleus of the PBN in rats in the GG group was significantly more robust than in the other three groups. These findings suggest a substantial alteration in orosensory-evoked neuronal response in this nucleus, due to sensory or motor deprivation during a critical developmental stage.

Effect of hydrocotarnine on cytochrome P450 and P-glycoprotein.

The injectable form of oxycodone contains hydrocotarnine that is supposed to potentiate the analgesic effect of oxycodone with unknown mechanism(s). In this study, the effects of hydrocotarnine on the cytochrome P450 (CYP) and P-glycoprotein (P-gp) were investigated. Hydrocotarnine did not induce a significant change in the metabolic activities of CYP2C9, 2C19, and 2E1 in an in vitro study using human CYP recombinants. Although weak inhibitory effects were observed on CYP3A4 and 2D6, these interactions did not seem to be clinically relevant. Hydrocotarnine also did not cause a significant change in the ATPase activity of human P-gp membranes, suggesting that it is not an inhibitor of P-gp. Furthermore, mice were intraperitoneally injected with hydrocotarnine for 14 days and the mRNA levels of major CYP isozymes and P-gp in the liver and small intestine were determined by real-time RT-PCR. As a result, none of the mRNAs investigated showed a significant change in their levels by hydrocotarnine treatment. In conclusion, it is unlikely that the potentiation of oxycodone effect by hydrocotarnine involves its effect on CYP and P-gp. The findings also demonstrate that hydrocotarnine is unlikely to cause drug interactions via CYP or P-gp.