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Background. Commercially available sugar-free chewing gums have been claimed to provide oral health benefits. Aim. The aim of this randomized, double-blind crossover in situ study was to compare the efficacy of three commercially available sugar-free chewing gums: Trident White, Orbit, and Orbit Professional, in remineralizing enamel subsurface lesions in situ. Design. Specimens containing enamel subsurface lesions were sectioned into test and control half-slabs with the test half-slabs inserted into removable palatal appliances. For each test chewing period, subjects were randomly allocated one of three test gums. Subjects (n = 10) chewed the randomly allocated gum for a 20-min period four times per day for 14 days. Each subject chewed all three test gums, with a 7-day washout period between crossovers. After each 14-day cycle, test and control half-slabs were paired, embedded in resin, sectioned, and subjected to microradiography to determine remineralization. Results. The gum TW produced significantly greater remineralization (18.4 +/- 0.9%) than Orbit (8.9 +/- 0.5%) and Orbit Professional (10.5 +/- 0.9%). Conclusion. The superior remineralization activity of the TW gum in situ was attributed to the presence of casein phosphopeptide-amorphous calcium phosphate nanocomplexes. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have examined racial and ethnic disparities in the use of selective serotonin reuptake inhibitors (SSRI). This study aims to examine the economic implications of these disparities.Research Design and Methods: In this retrospective observational study, the study sample was adult survey respondents with a diagnosis of depression from the Medical Expenditure Panel Survey (2002-2003). SSRI use was measured as the number of times when SSRIs were obtained. The racial and ethnic disparities in SSRI use were examined employing a negative binomial model. The economic implications of disparities were explored using a linear regression with SSRI use as an independent variable. Interaction terms between the variable for SSRI use and dummy variables for racial and ethnic groups were included to explore whether the relationships between SSRI use and health expenditures differ across racial and ethnic groups.Results: The mean number of times of SSRI use was higher for non-Hispanic whites than non-Hispanic blacks (3.02 vs. 1.79; p < 0.05) and Hispanic whites (3.02 vs. 1.68; p < 0.05). These differences were still significant after adjusting for covariates (p < 0.05). In the multivariate analysis, each time of SSRI use was associated with health expenditures of $301 higher. Neither dummy variables for racial and ethnic groups nor the interaction terms between these dummy variables and the variable for SSRI use were significant.Conclusions: The lower use of SSRIs among minorities compared to non-Hispanic whites is associated with lower health expenditures among minorities. SSRI may be a proxy for improved access to health care due to under-treatment of depression in general. The main limitation of this study is that its observational nature does not allow the researchers to determine whether the association between SSRI use and the increase in health expenditures is a causal effect. [ABSTRACT FROM AUTHOR]

Assessment of enamel subsurface lesion remineralisation is essential for the evaluation of novel remineralisation technologies. The gold standard to assess subsurface mineral gain of enamel lesions is transverse microradiography (TMR). However, some studies have utilised surface microhardness (SMH) to evaluate efficacy of remineralisation agents. The aim of this study was to assess remineralisation of enamel subsurface lesions using TMR and SMH after in vitro treatment with calcium-containing technologies, and to test correlation between the TMR and SMH measurements. The parameters obtained from the TMR and SMH analyses of enamel subsurface remineralisation were not significantly correlated. Furthermore, the enamel subsurface remineralisation as measured by TMR was significantly correlated with the water-soluble calcium concentration of the remineralisation products. Scanning electron microscopy revealed surface precipitates formed by specific remineralisation treatments obfuscated accurate assessment of remineralisation by SMH. It was concluded that TMR is a more appropriate method for analysis of enamel subsurface remineralisation, and that SMH values of remineralised enamel should be interpreted with caution. Using TMR the level of remineralisation (%R) by the different technologies was CPP-ACP/F (31.3 ± 1.4%); CPP-ACP (24.2 ± 1.4%); CaSO 4 /K 2 HPO 4 /F (21.3 ± 1.4%); f-TCP/F (20.9 ± 1.0%); Nano-HA/F (16.3 ± 0.3%); Nano-HA (15.3 ± 0.6%) and F alone control (15.4 ± 1.3%)., (© 2022. The Author(s).)

Calcium added to dentifrices can complex with fluoride ions to reduce intra-oral bioavailability and therefore efficacy in preventing dental caries. Six commercially available dentifrices containing different types of calcium and fluoride were analyzed for total and bioavailable fluoride levels by adding 10 g of dentifrice to 30 mL of distilled deionized water and mixing vigorously for 1 min to simulate toothbrushing. One milliliter of the dentifrice/water slurry was immediately centrifuged and the supernatant removed for bioavailable fluoride analysis and the mixed slurry prior to centrifugation used for total fluoride analysis using a modified microdiffusion method. The concentration of fluoride was determined using a fluoride ion-selective electrode calibrated with internal fluoride standards. All the dentifrices had similar total fluoride concentrations to those indicated on their labels (94% to 105%). However, only one dentifrice that contained calcium in the form of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) had almost 100% (97%) of fluoride in bioavailable form. The other dentifrices contained calcium carbonate and they exhibited significantly (p < 0.001) lower bioavailable fluoride levels (27% to 61%), through the generation of poorly soluble fluoride phases. The saliva biomimetic CPP, as CPP-ACP, in a dentifrice stabilised calcium and fluoride ions to maintain fluoride's bioavailability.

Remineralisation of demineralised enamel subsurface lesions can be enhanced by pretreatment of the lesions with base (NaOH). The aim of this study was to test the effect of intralesion pH modulation on remineralisation of demineralised enamel subsurface lesions by casein phosphopeptide-stabilised amorphous calcium fluoride phosphate (CPP-ACFP) in vitro. Two remineralisation models were utilised, the first involving 60-min cyclic pH modulation for 105 h and the second involved short-term cyclic pH modulation (12-min cycle, 240 min total duration) compared with the equivalent time of continuous treatment (200 min total duration). The intralesion pH modulation was achieved by cyclic exposure to a pH 12.9 NaOH solution and a CPP-ACFP remineralisation solution at pH 5.5. Percent remineralisation was assessed using transverse microradiography with data statistically analysed using a 2-sample Student t test. For the first model, the intralesion pH modulation group had significantly (p < 0.001) higher remineralisation (43.8 ± 6.9%) than the control group (28.2 ± 5.8%) cycled with water. For the second model, the intralesion pH modulation group had significantly (p < 0.001) higher remineralisation (23.1 ± 3.4%) than the group with continuous equivalent CPP-ACFP treatment time (1.9 ± 1.3%). In both models, intralesion pH modulation significantly accelerated remineralisation, and this was attributed to the effect pH modulation had on the diffusion gradients of ions/ion pairs and the degree of saturation with respect to apatite phases within the lesion fluid., (© 2021 S. Karger AG, Basel.)

Objectives: The aim of this study was to investigate the capacity of an approved food additive with anticariogenic properties, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), when added to a processed, sugar-containing yogurt with added lactic-acid bacteria (probiotics), to prevent demineralization of enamel subsurface lesions in vitro., Methods: Enamel subsurface demineralised lesions were created in thirty extracted human third molars. These were then exposed to artificial saliva (AS) with: 1) Danone yogurt alone; 2) Danone yogurt with 0.2 % w/w CPP-ACP; or 3) Danone yogurt with 0.5 % w/w CPP-ACP at 37 °C for two weeks. The yogurt/AS was replaced with fresh preparations each day. At the completion of each treatment the enamel slabs were embedded, sectioned and analyzed using transverse microradiography to measure changes in enamel lesion depths and subsurface mineral content. Yogurt samples were analysed for soluble calcium (Ca) and inorganic phosphate (Pi) levels and pH., Results: Yogurt alone demineralized enamel subsurface lesions to produce significantly larger lesions. However, the addition of 0.2 % CPP-ACP to the yogurt resulted in significant reduction in demineralization compared with yogurt alone (p < 0.0001). The addition of 0.5 % CPP-ACP to the yogurt produced a net remineralization effect with a significant increase in lesion mineral content (p < 0.0001). The addition of CPP-ACP resulted in a significant (p < 0.0001) dose-related increase in Ca, Pi and pH., Conclusions: The addition of CPP-ACP to a commercial yogurt exhibited a dose related protective effect with 0.5 % CPP-ACP producing remineralization of existing enamel subsurface lesions under the in vitro experimental conditions. CLINICAL SIGNIfiCANCE: The results of this study suggest that some processed yogurts with added sugar could result in enamel demineralization when frequently consumed by individuals with poor oral hygiene. The addition of CPP-ACP to these yogurts may help prevent demineralization and promote enamel subsurface lesion remineralization, and therefore, make them safer for teeth., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To assess the effect of CPP-ACP/F recharging on ion release and hardness of GIC Fuji-Triage (VII) and Fuji-Triage-EP (VII-EP) containing CPP-ACP/F., Methods: CPP-ACP distribution in Fuji-Triage-EP was determined using immunofluorescence. Thirty blocks of Fuji-Triage and Fuji-Triage-EP with the same surface area were placed individually in 5mL of 50mM lactic acid (pH 5) for three days. Every 12h ten Fuji-Triage and ten Fuji-Triage-EP blocks were treated with 2mL of either MI Paste Plus (CPP-ACP/F) solution (1g paste+4mL water), Placebo MI paste solution (no CPP-ACP/F), or distilled water for 2min. After each 2min treatment the blocks were rinsed with distilled water and placed back into the acid. Calcium, inorganic phosphate and fluoride levels in the acid solution were measured using atomic absorption spectrophotometry, colorimetry and ion specific electrode respectively. Vickers surface hardness of the GIC was also determined. Data were analysed using a two-sample t-test and one-way ANOVA with a Bonferroni-Holm correction for multiple comparisons., Results: CPP-ACP was distributed throughout Fuji-Triage-EP. Significantly (p<0.001) higher calcium, inorganic phosphate and fluoride ion release and greater surface hardness (acid resistance) was observed in both GIC's treated with the CPP-ACP/F paste. Fuji-Triage-EP released higher ion levels and exhibited greater surface hardness (acid resistance) than Fuji-Triage., Significance: Topical application of CPP-ACP/F paste to GIC Fuji-Triage-EP recharged ion release and increased surface hardness (acid resistance) which may help improve properties and resistance to degradation as well as improve ion release for caries control., (Copyright © 2020 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)

The approach to nasal reconstruction is based on the nature of the defect and the donor tissue. The Rintala flap, first described by Rintala and Asko-Slejavaara, is a surgical technique used to close midline nasal defects. It is a simple, one-stage procedure and is most effective for defects ranging from 1.5 to 2.5 centimeters. In addition, the Rintala flap is an excellent tissue match and maintains the natural contour of the nose. Other flaps employed in nasal defect closure include the paramedian forehead flap and the Rieger flap. The authors discuss the Rintala flap technique and utility with comparison to alternative flaps used for nasal reconstruction.

Accumulated intra-lesion protein such as serum albumin has been speculated to impede remineralisation of carious enamel lesions. The aim of this study was to assess whether intra-lesion bovine serum albumin (BSA) affected subsequent remineralisation of enamel subsurface lesions. Confocal microscopy was used to confirm localisation of BSA in artificial enamel subsurface lesions and its subsequent degradation by a high pH sodium hypochlorite treatment. An in vitro remineralisation experiment tested the effect of intra-lesion BSA, and its degradation by sodium hypochlorite, on remineralisation of subsurface lesions by casein phosphopeptide stabilised amorphous calcium fluoride phosphate. In addition, lesions without BSA were pre-treated with one of 2 high pH solutions (sodium hypochlorite or sodium hydroxide) prior to remineralisation to test whether the high pH pre-treatment influenced remineralisation. Data were obtained on remineralisation using transverse microradiography and were analysed with a one-way ANOVA. Intra-lesion BSA had no significant effect on remineralisation compared with that of control lesions. Pre-treatment of BSA-containing lesions with sodium hypochlorite significantly increased remineralisation. The lesions without BSA that were pre-treated with either sodium hypochlorite or sodium hydroxide also showed the same level of remineralisation as the BSA-containing lesions pre-treated with sodium hypochlorite indicating that the increased remineralisation was pH related. Hence, it was concluded that intra-lesion BSA did not affect remineralisation of artificial enamel subsurface lesions in this model system and that a high pH pre-treatment enhanced remineralisation., (© 2019 S. Karger AG, Basel.)

Objectives: To determine if chewing gum containing casein phosphopeptide stabilised amorphous calcium phosphate (CPP-ACP) promoted an increase in the abundance of Streptococcus sanguinis and other species associated with dental health in supragingival plaque in a clinical study., Materials and Methods: Nineteen participants were recruited for a three-leg cross-over, randomised, controlled clinical trial. Participants chewed a sugar-free gum with or without CPP-ACP six times daily for 20 min over two weeks. The study also involved no gum chewing (no gum) for the same two week period. Participants were randomly assigned to one of the test gums or no gum for each intervention period. Participants abstained from oral hygiene and had washout periods of two weeks between intervention periods. After each intervention period, supragingival plaque was collected and analysed for bacterial composition by sequencing the V4 variable region of the 16S rRNA gene. Data were analysed using a linear mixed model., Results: The CPP-ACP gum intervention produced a significant (p < 0.01) increase in the proportions of S. sanguinis (112%), as well as the commensal species Rothia dentocariosa (127%), Corynebacterium durum (80%) and Streptococcus mitis (55%) when compared with the no gum intervention. All the species that were promoted by the CPP-ACP gum are known to possess one or both of the alkali-producing enzymes arginine deiminase and nitrate reductase., Conclusion: This clinical study demonstrated that chewing a sugar-free gum containing CPP-ACP promoted prebiosis by significantly increasing the proportion of S. sanguinis and other health-associated bacterial species in supragingival plaque., Clinical Significance: Regular chewing of CPP-ACP sugar-free gum increases the proportions of health-associated commensal species in supragingival plaque to promote prebiosis and oral homeostasis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Soy beverages are promoted as healthy alternatives to bovine milk even though they can contain added sugar., Objectives: To compare enamel mineral content after consumption of bovine milk or a soy beverage in a double-blind, randomized, cross-over in situ clinical study., Materials and Methods: Human enamel slabs with subsurface lesions were prepared and inserted into intra-oral appliances worn by volunteers who consumed 200 ml of either bovine milk or a soy beverage over a 60 s period once a day for 15 days. Enamel lesion depth and mineral content were measured using transverse microradiography. Saliva samples were collected immediately after consuming the beverages and calcium, inorganic phosphate and fluoride levels analysed. Data were statistically analysed using a linear mixed model., Results: Depth of the enamel subsurface lesions increased by 7.1 ± 2.0 μm and mineral content decreased by 47 ± 22 vol% min.μm after consumption of the soy beverage indicating demineralization. However, after consumption of bovine milk the depth of the lesions decreased by 7.6 ± 3.5 μm and mineral content increased by 202 ± 43 vol% min.μm indicating remineralization. The changes were significantly different (p < 0.001) between the two beverages. Fluoride levels were similar in the saliva samples for both beverages, however the calcium and inorganic phosphate levels for the bovine milk group were significantly higher (p < 0.02) than those for the soy beverage group., Conclusions: In this randomized, double-blind in situ clinical trial consumption of a soy beverage demineralized enamel whereas bovine milk produced remineralization., Clinical Significance: Although soy beverages are promoted as healthy alternatives to bovine milk the added sugar and low calcium bioavailability of the soy drink makes frequent consumption a caries risk. (Trial registration no. ISRCTN19137849)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to investigate the effect of treatment with the saliva biomimetic, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and SnF 2 /NaF compared with SnF 2 /NaF alone on coronal surface caries progression in head-and-neck cancer patients undergoing radiotherapy., Methods: Twenty-four participants were randomized into two groups. Both groups used 0.4% SnF 2 gel and a 0.32% NaF toothpaste; the test group also applied a crème containing 10% CPP-ACP three times daily while the control group used an identical crème without CPP-ACP (placebo). Resting saliva flow rate and saliva fluoride concentrations were determined. Caries status was assessed using ICDASII at baseline and 12-weeks postradiotherapy. Data were statistically analysed using a linear mixed effects model., Results: Both groups showed significantly reduced resting saliva flow rate (P < 0.001) postradiotherapy. There were no significant differences in flow rates and fluoride concentration between groups. The CPP-ACP group exhibited a significant (P < 0.05) 51% reduction in coronal surface caries progression compared with the placebo group., Conclusion: Resting salivary flow rate was significantly reduced in head-and-neck cancer patients following radiotherapy and use of CPP-ACP with SnF 2 /NaF significantly lowered caries progression compared with SnF 2 /NaF alone., (© 2018 Australian Dental Association.)

Dental caries, erosion and hypersensitivity are major public health problems. SnF 2 is used widely in oral care products to help prevent/treat these conditions. Casein phosphopeptide-stabilised amorphous calcium phosphate nanocomplexes (CPP-ACP) are a biomimetic nanotechnology of salivary phosphopeptide-ACP complexes that deliver bioavailable calcium and phosphate ions to promote dental remineralisation (repair). We show here using in vitro studies and a double-blind, randomised controlled, cross-over design in situ clinical trial that SnF 2 and CPP-ACP interact to form a nanofilament coating on the tooth surface and that together they are superior in their ability to promote dental remineralisation. Sn(II) by cross-linking the CPP-ACP helps to stabilise the complexes which improves delivery to the tooth surface and enhances binding and ion incorporation into tooth mineral. The combination of SnF 2 and CPP-ACP in oral care products may significantly improve their efficacy in prevention/treatment of dental caries/erosion and hypersensitivity.

Dental caries is associated with plaque dysbiosis, leading to an increase in the proportions of acidogenic and aciduric bacteria at the expense of alkali-generating commensal species. Stannous fluoride (SnF 2 ) slows the progression of caries by remineralization of early lesions but has also been suggested to inhibit glycolysis of aciduric bacteria. Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) promotes fluoride remineralization by acting as a salivary biomimetic that releases bioavailable calcium and phosphate ions, and the peptide complex has also been suggested to modify plaque composition. We developed a polymicrobial biofilm model of caries using 6 bacterial species representative of supragingival plaque that were cultured on sound human enamel and pulsed with sucrose 4 times a day to produce a high cariogenic challenge. We used this model to explore the mechanisms of action of SnF 2 and CPP-ACP. Bacterial species in the biofilms were enumerated with 16S rRNA gene sequence analyses, and mineral loss and lesion formation were determined in the enamel directly under the polymicrobial biofilms via transverse microradiography. The model tested the twice-daily addition of SnF 2 , CPP-ACP, or both. SnF 2 treatment reduced demineralization by 50% and had a slight effect on the composition of the polymicrobial biofilm. CPP-ACP treatment caused a similar inhibition of enamel demineralization (50%), a decrease in Actinomyces naeslundii and Lactobacillus casei abundance, and an increase in Streptococcus sanguinis and Fusobacterium nucleatum abundance in the polymicrobial biofilm. A combination of SnF 2 and CPP-ACP resulted in a greater suppression of the acidogenic and aciduric bacteria and a significant 72% inhibition of enamel demineralization.

Porphyromonas gingivalis , the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer's disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer's patients, and levels correlated with tau and ubiquitin pathology. Oral P. gingivalis infection in mice resulted in brain colonization and increased production of Aβ 1-42 , a component of amyloid plaques. Further, gingipains were neurotoxic in vivo and in vitro, exerting detrimental effects on tau, a protein needed for normal neuronal function. To block this neurotoxicity, we designed and synthesized small-molecule inhibitors targeting gingipains. Gingipain inhibition reduced the bacterial load of an established P. gingivalis brain infection, blocked Aβ 1-42 production, reduced neuroinflammation, and rescued neurons in the hippocampus. These data suggest that gingipain inhibitors could be valuable for treating P. gingivalis brain colonization and neurodegeneration in Alzheimer's disease.

Objectives: To compare remineralization of enamel subsurface lesions by fluoride dentifrices with added calcium in a double-blind, randomized, cross-over, in situ study., Methods: Human enamel with subsurface lesions were prepared and inserted into intra-oral appliances worn by volunteers. A slurry (1 g toothpaste/4 ml H 2 O) was rinsed for 60 s, 4 times per day for 14 days. Seven toothpastes were tested: (i) 1450 ppm F (NaF), (ii) 5000 ppm F (NaF), (iii) 1450 ppm F (MFP) with calcium sodium phosphosilicate (CSP), (iv) 1450 ppm F (MFP) with CaCO 3 /Arg, (v) 1150 ppm F (SnF 2 ) with amorphous calcium phosphate (ACP), (vi) 1100 ppm F (NaF) with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and (vii) 5000 ppm F (NaF) with functionalized tri-calcium phosphate (TCP). Total (acid soluble) and bioavailable (water soluble) calcium, inorganic phosphate and fluoride levels of the dentifrices were measured using ion chromatography (F/MFP) and spectrophotometry (Ca and inorganic phosphate). Enamel lesion mineral content was measured using transverse microradiography. Data were statistically analysed using a linear mixed model., Results: All calcium and fluoride containing toothpastes released > 90% of bioavailable fluoride and were superior to the respective fluoride alone toothpastes in remineralization of enamel subsurface lesions. The level of remineralization followed the order: CPP-ACP/1l00 ppm F > ACP/1150 ppm F = TCP/5000 ppm F > 5000 ppm F = CaCO 3 /Arg/1450 ppm F = CSP/1450 ppm F > 1450 ppm F. Bioavailable calcium levels significantly correlated with enhanced remineralization of enamel subsurface lesions., Conclusions: Bioavailable calcium in fluoride dentifrices enhanced remineralization of enamel subsurface lesions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Conventional DNA replication is initiated from specific origins and requires the synthesis of RNA primers for both the leading and lagging strands. In contrast, the replication of yeast mitochondrial DNA is origin-independent. The replication of the leading strand is likely primed by recombinational structures and proceeded by a rolling circle mechanism. The coexistent linear and circular DNA conformers facilitate the recombination-based initiation. The replication of the lagging strand is poorly understood. Re-evaluation of published data suggests that the rolling circle may also provide structures for the synthesis of the lagging-strand by mechanisms such as template switching. Thus, the coupling of recombination with rolling circle replication and possibly, template switching, may have been selected as an economic replication mode to accommodate the reductive evolution of mitochondria. Such a replication mode spares the need for conventional replicative components, including those required for origin recognition/remodelling, RNA primer synthesis and lagging-strand processing., (Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)