Prediction of Future Caries in 1-Year-Old Children via the Salivary Microbiome.

Dental caries is the most common chronic disease in children that causes negative effects on their health, development, and well-being. Early preventive interventions are key to reduce early childhood caries prevalence. An efficient strategy is to provide risk-based targeted prevention; however, this requires an accurate caries risk predictor, which is still lacking for infants before caries onset. We aimed to develop a caries prediction model based on the salivary microbiome of caries-free 1-y-old children. Using a nested case-control design within a prospective cohort study, we selected 30 children based on their caries status at 1-y follow-up (at 2 y old): 10 children who remained caries-free, 10 who developed noncavitated caries, and 10 who developed cavitated caries. Saliva samples collected at baseline before caries onset were analyzed through 16S rRNA gene sequencing. The results of ß diversity analysis showed a significant difference in salivary microbiome composition between children who remained caries-free and those who developed cavitated caries at 2 y old (analysis of similarities, Benjamini-Hochberg corrected, P = 0.042). The relative abundance of Prevotella nanceiensis, Leptotrichia sp. HMT 215, Prevotella melaninogenica, and Campylobacter concisus in children who remained caries-free was significantly higher than in children who developed cavitated caries (Wilcoxon rank sum test, P = 0.024, 0.040, 0.049, and 0.049, respectively). These taxa were also identified as biomarkers for children who remained caries-free (linear discriminant analysis effect size, linear discriminant analysis score = 3.69, 3.74, 3.53, and 3.46). A machine learning model based on these 4 species distinguished between 1-y-old children who did and did not develop cavitated caries at 2 y old, with an accuracy of 80%, sensitivity of 80%, and specificity of 80% (area under the curve, 0.8; 95% CI, 44.4 to 97.5). Our findings suggest that these salivary microbial biomarkers could assist in predicting future caries in caries-free 1-y-old children and, upon validation, are promising for development into an adjunctive tool for caries risk prediction for prevention and monitoring.

Effect of Vital Tooth Bleaching on Surface Roughness and Streptococcal Biofilm Formation on Direct Tooth-Colored Restorative Materials.

OBJECTIVE: To compare the effect of simulated bleaching with a 10% carbamide peroxide (CP) or a 40% hydrogen peroxide (HP) system on surface roughness of resin composite and resin-modified glass ionomer cement (RMGI) and streptococcal biofilm formation on these surfaces. METHODS AND MATERIALS: Specimens of nanofilled resin composite and RMGI (n=108 each) were randomly divided into three groups (n=36 each): no treatment control, 10% CP, and 40% HP. The surface roughness values (Ra) were measured before and after treatments. The specimens in each group were randomly divided into three subgroups (n=12) and incubated with Streptococcus mutans, Streptococcus sanguinis, and trypticase soy broth control for 24 hours. Biofilm formation was quantified by crystal violet staining, and the structure was visualized by scanning electron microscopy. The differences between the mean changes in Ra between the 10% CP and 40% HP groups of each material were evaluated with an independent t-test. The quantity of biofilm formation on each material was analyzed with one-way analysis of variance with the post hoc Tukey test ( α=0.05). RESULTS: Surface roughness significantly increased after bleaching in all groups. There was no significant difference between the 10% CP and 40% HP groups of each material. For S. mutans biofilm formation, bleaching with 10% CP and 40% HP increased biofilm on both materials compared to controls. However, S. sanguinis biofilm formation was significantly higher on bleached resin composite but not on RMGI specimens. CONCLUSIONS: Simulated bleaching with 10% CP or 40% HP increased both surface roughness and biofilm formation on resin composite and RMGI, except for S. sanguinis biofilm on RMGI.

The pharmacokinetics of oral dihydroartemisinin and artesunate in healthy Thai volunteers.

The pharmacokinetics of oral dihydroartemisinin (DHA) following the dose of 2 and 4 mg/ kg body weight dihydroartemisinin (Twisinin, T-2 Program, Thailand) and 4 mg/kg body weight oral artesunate (AS; Guilin Pharmaceutical Works, Guangxi, China) were investigated in 20 healthy Thai volunteers (10 males, 10 females). All formulations were generally well tolerated. Oral DHA was rapidly absorbed from gastrointestinal tract with marked inter-individual variation. The pharmacokinetics of DHA following the two dose levels were similar and linearity in its kinetics was observed. Based on the model-independent pharmacokinetic analysis, median (95% CI) values for Cmax of 181 (120-306) and 360 (181-658) ng/ml were achieved at 1.5 hours following 2 and 4 mg/kg body weight dose, respectively. The corresponding values for AUC0-infinity, t1/2z, CL/f and Vz/f were 377 (199-1,128) vs 907 (324-2,289) ng.h/ml, 0.96 (0.70-1.81) vs 1.2 (0.75-1.44) hours, 7.7 (4.3-12.3) vs 6.6 (3.1-10.1) l/kg, and 90.5 (28.6-178.2) vs 6.6 (3.1-10.1) ml/min/kg, respectively (2 vs 4 mg/kg dose). Oral AS was rapidly biotransformed to DHA, which was detectable in plasma as early as 15 minutes of AS dosing. Following 4 mg/kg dose, median (95% CI) value for Cmax of 519 (236-284) ng/ml was achieved at 0.7 (0.25-1.5) hours. AUC0-infinity, and t1/2z were 657 (362-2,079) ng.h/ml, 0.74 (0.34-1.42) hours, respectively. Cmax of DHA following oral AS were significantly higher, but total systemic exposure was greater following oral DHA at the same dose level (4 mg/kg body weight). There was no significant sex difference in pharmacokinetics of DHA.

Bromodomain factor 1 corresponds to a missing piece of yeast TFIID.

The basal transcription factor TFIID consists of the TATA-binding protein (TBP) and TBP-associated factors (TAFs). Yeast Taf67 is homologous to mammalian TAF(II)55. Using a yeast two-hybrid screen to identify proteins that interact with Taf67, we isolated Bromodomain factor 1 (Bdf1) and its homolog (Bdf2). The Bdf proteins are genetically redundant, as cells are inviable without at least one of the two BDF genes. Both proteins contain two bromodomains, a motif found in several proteins involved in transcription and chromatin modification. The BDF genes interact genetically with TAF67. Furthermore, Bdf1 associates with TFIID and is recruited to a TATA-containing promoter. Deletion of Bdf1 or the Taf67 Bdf-interacting domain leads to defects in gene expression. Interestingly, the higher eukaryotic TAF(II)250 has an acetyltransferase activity, two bromodomains, and an associated kinase activity. Its yeast homolog, Taf145, has acetyltransferase activity but lacks the bromodomains and kinase. Bdf1, like TAF(II)250, has a kinase activity that maps carboxy-terminal to the bromodomains. The structural and functional similarities suggest that Bdf1 corresponds to the carboxy-terminal region of higher eukaryotic TAF(II)250 and that the interaction between TFIID and Bdf1 is important for proper gene expression.

CD28 receptor endocytosis is targeted by mutations that disrupt phosphatidylinositol 3-kinase binding and costimulation.

Although the lipid kinase phosphatidylinositol 3-kinase (PI-3K) binds at high levels to the cytoplasmic tail of CD28, controversy exists regarding its role in CD28 costimulation. Potentially, the kinase could be linked to a signaling cascade or be needed indirectly in events such as receptor endocytosis. Indeed, little is known regarding both the fate of CD28 following receptor ligation and the events that control the process. In this study, we help to resolve this issue by providing evidence that PI-3K plays a role in regulating CD28 endocytosis. We show that approximately 25 to 35% of wild-type CD28 becomes endocytosed following Ab binding (t1/2 = 10 min), followed by segregation into two pools; one pool is destined for degradation in lysosomal compartments and is blocked by chloroquine, and another pool that is recycled to the cell surface (t1/2 = 2.5 h). Recycling of CD28 could have an important impact on CD80/86-mediated costimulation by replenishing functionally active receptors on the cell surface. Several findings implicate PI-3K in the control of endocytosis. Modulation experiments indicate that CD28-PI-3K complexes are preferentially endocytosed, and mutations that alter PI-3K binding concordantly affect the efficacy of endocytosis. Importantly, mutations that inhibit receptor internalization also block cosignaling. Therefore, previous results documenting a requirement for PI-3K may be explained by a blockage of receptor internalization.

Effect of diazepam and phenobarbital sodium on postcoital contraceptive efficacy of ethinyl estradiol in rats.

Diazepam, a well known tranquilizer, and ethinyl estradiol have frequently been prescribed together in rape cases. These two drugs were reported to possess an opposite action on uterine motility. Phenobarbital, a typical enzyme inducer, has been prescribed together with ethinyl estradiol in some cases as a sedative-hypnotic. The present study was, therefore, designed to investigate the possible interferences of diazepam or phenobarbital sodium on postcoital contraceptive efficacy of ethinyl estradiol (4 micrograms/kg/day) in rats. All tested doses of diazepam (1, 2 and 4 mg/kg/day) or phenobarbital sodium (30 and 60 mg/kg/day) appear to have no effect on the efficacy of ethinyl estradiol when either of them was administered from D3 to D5 or from D1 to D5 of pregnancy. In addition, neither diazepam nor phenobarbital sodium at the highest doses used showed an effect on pregnancy.

Role of adrenal steroids on the cardiac c-AMP response to isoprenaline in the rat.

The effect of adrenalectomy on the basal cardiac c-AMP level and the elevated c-AMP level induced by intravenous administration of isoprenaline (10 mcg/kg) were determined by radio-protein assay. The basal cardiac c-AMP level was not altered by adrenalectomy. But the cardiac c-AMP responses to isoprenaline was significantly less in adrenalectomized rats, maintained with 1% sodium chloride solution for one week; this effect, however, disappeared when animals were maintained for 2 or 4 weeks. This could not be restored by acute administration of dexamethasone (100 mcg/rat). The possible reasons for these effects of adrenalectomy are discussed.

The effect of D-norgestrel, 30 micrograms, on the oral glucose tolerance test, including insulin levels, in Thai women.

The effect of D-norgestrel, 30 mug, on the oral glucose tolerance test was studied in 49 Thai women. There was a significant elevation of the blood glucose level at 60 minutes during the test in women who had taken D-norgestrel for 6 and 12 months. Insulin levels in the blood were significantly elevated over control levels in both groups of women at 90, 120, 150, and 180 minutes during the test. There was no difference in the results obtained at 6 months and 12 months. There was also no significant difference in the fasting blood glucose or insulin levels in the three groups of women. The results indicate that D-norestrel at a daily dose of 30 mug has an effect on carbohydrate metabolism in Thai women.

PIP: Oral glucose tolerance tests were performed on 49 Thai women to inve stigate the effect of d-norgestrel (30 mcg) on carbohydrate metabolism. At 60 minutes, women who had taken d-norgestrel for 6 and 12 months showed a significant increase in blood glucose levels (p less than .05). There was a significant increase in blood insulin levels at 90, 120, 150, and 180 minutes in both groups (p less than .05). However, fa sting blood glucose or insulin levels were not markedly different. It is concluded that d-norgestrel, at the dose studied, affects carbohydrat e metabolism in Thai women, and it is suggested that this may be a characteristic effect of 19-nor steroids.