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Objectives: to investigate whether baseline mineral distribution modulates the ability of silver diammine fluoride (SDF) to remineralize and stain enamel caries lesions., Methods: This laboratory study followed a 3 [treatment: SDF/fluoride varnish (FV)/deionized water (DIW)] ×3 [lesion protocol: methylcellulose (MeC)/hydroxyethylcellulose (HEC)/Carbopol 907 (C907)] factorial design. Lesions were created in bovine enamel specimens (n = 20). Treatments were applied and lesions remineralized in artificial saliva. Digital transverse microradiography (TMR-D) was used to analyze lesions. Lesion color was monitored spectrophotometrically. The effects of lesion protocol and treatment on changes in lesion depth (ΔLD), mineral loss (ΔΔZ), maximum mineral density at the surface zone (ΔSZ max ), and color changes related to remineralization (ΔL* remin ) were analyzed using two-way ANOVA., Results: The treatment×lesion protocol interaction was significant for ΔΔZ (p < 0.01) and ΔL* remin (p < 0.01), however not for ΔLD (p = 0.23) or ΔSZ max (p = 0.91). There were no differences in ΔΔZ between treatments in HEC and C907 lesions. However, DIW resulted in more remineralization than both SDF (p < 0.01) and FV (p = 0.01) in MeC lesions. Considering changes from lesion baseline after remineralization in MeC lesions, SDF treatment resulted in the highest mineral gain in the surface zone. However, DIW revealed the highest mineral gain after remineralization in the lesion body. SDF stained lesions with the intensity increasing after remineralization in C907 lesions, whereas staining decreased in MeC and HEC lesions., Conclusion: High fluoride treatments can interfere with continuous remineralization of caries lesions due to partial arrest. Baseline lesion mineral distribution affects SDF's ability to enhance remineralization and the staining caused by SDF., Clinical Significance: SDF is being used to arrest active caries lesions extending into dentin and to treat dentin hypersensitivity. This study shed light on SDF's effect on an isolated process in dental caries only, remineralization. It achieved this by examining enamel caries lesions with differing mineral distributions and assessing their staining properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Assessed the effect of dental products containing nano-hydroxyapatite (nano-HA) + fluoride on the remineralization of white spot lesions (WSL) in vivo or in situ., Methods: Seven databases were explored using a two-pronged approach (intervention/treatment). After screening, full-text assessment, and further exclusion, the qualitative synthesis of five studies (four clinical and one in situ) was performed. Based on the Cochrane collaboration guidelines relevant data of the studies were collected and summarized. The Cochrane risk of bias tool for randomized trials (RoB 2.0) was used to appraise the studies' methodological quality and the GRADE guidelines to assess their level of evidence. The RoB 2.0 domains were rated on their risk of bias (RoB) as low, high, or with some concerns, and an adaptation of the tool was used to the in situ study., Results: The included studies assessed 151 WSL in anterior permanent teeth, on patients with varying ages. The protocol application, treatment length (7d-12 w), and control groups varied greatly between the studies making the performance of a quantitative analysis unfeasible. The general RoB of the clinical studies was classified as being of low risk (n = 2) or some concerns (n = 2). The in situ study was considered as being of low risk. The level of the evidence was moderate. Most of the studies found moderate evidence regarding the superiority of this association in clinical settings., Conclusion: Even with the nano-HA + fluoride promising results for the remineralization treatment of WSL, due to the restricted number of studies and types of products, its extended use cannot be recommended based on the current systematic review, especially when considering the moderate level of the evidence found., Clinical Significance: Due to the biocompatibility and higher surface coverage of nano-HA and the remineralization capacity of fluoride formulations, the association of these elements to remineralize WSL has been positively reported. After the collection and qualitative appraise of the data, the clinical evidence of the use of these dental products is promising but limited., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To assess the clinical evidence for silver diamine fluoride (SDF) to reduce dentine hypersensitivity in adults., Methods: Two independent researchers searched the English literature in five databases (Scopus, PubMed, Web of Science, EMBASE and the Cochrane Library) up to 15th July 2023 for clinical trials investigating the desensitising effect of professionally applied SDF to manage dentine hypersensitivity in adults aged 18 or above at any follow-up period. The primary outcome was the change in dentine hypersensitivity between baseline and follow-up visits after SDF application regarding any validated pain outcome measures. The Cochrane guidelines were used for the risk of bias assessment., Results: Three hundred and thirty-one studies were identified, and four of them were finally included. Three of the included studies were rated as having a 'low risk' of bias. The SDF solution reduced dentine hypersensitivity in adults. The percentage reduction in dentine hypersensitivity ranged from 23 % to 56 % after a single application of SDF solution. Moreover, the SDF solution was more effective than potassium nitrate, potassium oxalate and glutaraldehyde plus hydroxyethyl methacrylate in reducing dentine hypersensitivity. Meta-analysis indicated a more significant reduction in visual analogue scales (1-10) by 1.35 (95 % CI:0.9-1.8; p<0.00001) after receiving the SDF application than controls., Conclusion: The included clinical trials showed that SDF solution reduced dentine hypersensitivity in adults. However, clinical trials are few, and their protocol varied from one another. Further well-designed clinical trials should be conducted to provide more evidence on its use to manage dentine hypersensitivity., Clinical Significance: SDF is cleared as desensitizing agents by the US Food and Drug Administration to manage dentine hypersensitivity, which induces pain, limits food choice, and impacts the quality of life. Evidence from this systematic review informs clinicians and provides researchers insight for future research on SDF use for dentine hypersensitivity. THE INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO) REGISTRATION NUMBER: CRD42023462613., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Untreated caries in primary teeth is one of the most prevalent health problems in children worldwide. Silver diamine fluoride (SDF) non-invasively arrests caries but causes staining unlike Nano Silver Fluoride (NSF) which causes no stains. This study compared the effect of NSF and 38 % SDF on the oral health related quality of life (OHRQoL) of preschool children after 6 months., Methods: Children were included if they were younger than 4 years, with at least one active lesion, ICDAS score ≥3, attending nurseries in a rural area in Alexandria, Egypt. They were randomly assigned to receive NSF once at baseline, or SDF at baseline and after 6 months. The Arabic version of the Early Childhood Oral Health Impact Scale (A-ECOHIS) was used to assess the OHRQoL. The groups were compared using chi-square test and the effect of the intervention on OHRQoL was assessed using multiple linear regression., Results: 360 children were included, mean (SD) age = 42.3 (8.2) months. After 6 months, NSF had significantly lower A-ECOHIS scores than SDF in bivariate analysis (p< 0.05) and in regression analysis (B= -5.02, p = 0.001) after adjusting for confounders. There were significant reductions in the A-ECOHIS total and domains' scores in both study groups, except for the social interaction domain in the SDF group., Conclusion: After 6-month, both agents significantly improved children's OHRQoL although NSF had a significantly better impact on OHRQoL than SDF., Clinical Significance: Patient-reported outcomes support the inclusion of the two agents among the options for ECC management with better effect on quality of life after NSF., Trial Registration: The trial was registered in the clinicaltrials.gov registry (#NCT05255913)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: This systematic review and network meta-analysis (NMA) aimed to establish a clinically relevant hierarchy of the different adhesive and/or restorative approaches to restore cavitated root caries lesions through the synthesis of available evidence., Materials and Methods: A systematic search was conducted in Medline/Web of Science/Embase/ Cochrane Library/Scopus/grey literature. RCTs investigating ≥2 restorative strategies (restorative /adhesive materials) for root caries lesions in adult patients were included. Risk of bias within studies was assessed (Cochrane&#95;RoB-2) and the primary outcome was survival rate of restorations at different follow-up times (6-/12-/24-months). Network meta-analyses were conducted using a random effects model stratified by follow-up times. I 2 -statistics assessed the ratio of true to total variance in the observed effects. All available combinations of adhesives (1-SE: one-step self-etch; 2-3ER: two-/three-step etch-and-rinse) and restorative materials (conventional composite (CC) as well as conventional and resin-modified glass ionomer cements (GIC, RMGIC)) were included. Risk of bias across studies and confidence in NMA (CINeMA) were assessed., Results: 547 studies were identified and nine were eligible for the NMA. In total, 1263 root caries lesions have been restored in 473 patients in the included clinical trials. Patients involved were either healthy (n = 6 trials), living in nursing homes (n = 1 trial) or received head-and-neck radiotherapy (n = 2 trials). There was statistically weak evidence to favour either of material/material combination regarding the survival rate. A tendency for higher survival rate (24-months) was observed for 2-3ER/CC (OR 24mths 2.65; 95% CI=1.45/4.84) as well as RMGIC (OR 24mths 2.05; 95% CI=1.17/3.61) compared to GIC. These findings were though not statistically significant and confidence of the NMA was low., Conclusion: An evidence-based choice of restorative strategy for managing cavitated root caries lesions is currently impossible. There is a clear need for more standardised, well-designed RCTs evaluating the retention rate of root caries restoration approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: To compare the level of acceptance of silver diamine fluoride (SDF) treatment between different functional groups of older adults aged 65-years-old and above., Methods: Three groups were recruited representing functionally-independent ("Community dwelling"), frail ("Nursing home"), and functionally-dependent older adults ("Caregiver": proxy respondent involved in caring for an older adult of all functional levels). Participants viewed a video on SDF and an interviewer-led questionnaire collected demographics, dental experience and perception on SDF use., Results: The study recruited 201 participants (100 "Community dwelling", 51 "Nursing home", 50 "Caregiver"). Overall, 73 % of participants were accepting of SDF treatment. Those in the "Community dwelling" group were most accepting (85 %), followed by the "Nursing home" group (61 %) and "Caregiver" group (60 %) (p<0.001). Participants were more accepting of SDF use on posterior (73 %) compared to anterior teeth (46 %). They were more accepting when SDF was presented as a treatment to avoid infection and pain (87 %), and general anesthesia (78 %). In a regression analysis, "Nursing home" and "Caregiver" participants were three times less likely to accept SDF (OR 0.27 [95 % CI: 0.13 to 0.60], and OR 0.27 [95 % CI: 0.12 to 0.58] respectively) compared to "Community dwelling" participants. After adjusting for other factors, only the "Caregiver" group remained significant (Adjusted OR 0.32 [95 % CI: 0.13 to 0.78])., Conclusions: Older adults were accepting of SDF and this treatment modality has the potential to be a routine treatment option in dental caries management in this population. However, this was less certain among frail and functionally dependent older adults., Clinical Significance: An SDF program to manage caries is likely to be well-received by functionally-independent older adults. However, the acceptance among frail and functionally-dependent older adults were lower even though SDF is mostly likely to benefit these populations. There is a need to investigate this relatively lower levels of acceptance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: This umbrella review comprehensively appraised the evidence on the use of compomers in comparison to other dental filling materials for restorative treatment of decayed primary teeth., Data: The literature search was conducted based on the question: "Is the use of compomers as a dental filling material more successful in the restorative treatment of decayed primary teeth than other dental filling materials?" No language restriction was applied and systematic reviews published up to May 2023 were included. The ROBIS tool was used to assess the methodological quality of the included systematic reviews. Data were extracted for narrative synthesis, considering the restoration failure/success outcomes., Search: Online search was conducted in three databases (PubMed/Medline, Embase and Cochrane library)., Study Selection: The electronic search yielded a total of 779 publications. Finally, 18 systematic reviews were included in this umbrella review. Four systematic reviews presented a low risk of bias, 11 presented an unclear risk of bias and three presented a high risk of bias. Most systematic reviews presenting low risk of bias reported no difference in the success rates of compomers compared to other dental filling materials used for restoration of decayed primary teeth. Studies that found a significant difference or that made clear recommendations towards the use of compomers were commonly rated with a high risk of bias., Conclusion: Compomers are similar to other dental filling materials for the placement of direct restorations in primary teeth., Clinical Significance: The results of this umbrella review indicate a similar clinical performance of compomers compared to other materials containing a resin component for direct restoration in primary teeth. Therefore, the choice of restorative material will depend on multiple factors, such as clinician's skills/preferences, patients' wishes, costs, and cavity type/location., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To compare the clinical performance (retention, secondary caries, marginal adaptation, marginal discoloration, and postoperative hypersensitivity) of self-adhesive flowable composite resins (SAFCs) and flowable composite resins (FCs) in permanent teeth with occlusal cavities., Data: Randomized controlled trials (RCTs) of SAFCs versus FCs with a follow-up length of at least one year. No restrictions were placed on language or publication date., Sources: Five databases, including PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials, were searched manually by browsing ten related journals. On 14 June 2023, all electronic and manual searches were updated., Study Selection: Five RCTs with 138 participants were included. Cochrane's risk of bias tool (2.0) was implemented in selected studies, and the GRADE tool was utilised to evaluate the evidence quality. To summarize the effects of the treatments and pool the data, a random-effects model was used., Conclusions: According to the modified United States Public Health Service Evaluation (USPHS) criteria, there was no discernible difference between the groups during the two-year follow-up period (maximum follow-up time). Nevertheless, FCs applied with the etch-and-rinse mode demonstrated superior marginal adaptation and marginal discoloration at the two-year follow-up (relative risk = 3.21 [1.50 to 6.83], 3.40 [1.10, 10.48]). The evidence for marginal discoloration at any recall time and marginal adaptation at the one-year follow-up was graded as moderate quality due to inconsistency. Moreover, low-quality evidence for marginal adaptation at two-year follow-up was due to imprecision and inconsistency., Clinical Significance: SAFCs exhibited clinical performance comparable to that of FCs in occlusal cavities. Further high-quality clinical trials are needed to provide solid evidence to support the clinical application of SAFCs., Registration: PROSPERO (CRD42022374983)., Competing Interests: Declaration of Competing Interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this randomised, controlled, split-mouth trial was to assess the masking results in initial caries lesions (ICL) that were either resin infiltrated or fluoridated during treatment with fixed orthodontic appliances., Methods: Adolescent patients (age range:12-18years) with fixed orthodontic appliances who had developed ICL [ICDAS 1 or 2 (International Caries Detection and Assessment System)] during orthodontic treatment were consecutively recruited and randomly assigned to either resin infiltration with up to 3 etching procedures (Group:Inf) or to 3-monthly application of a fluoride varnish (Group:FV). Both interventions were performed according to the manufacturer's recommendations. Primary and secondary outcomes (ΔE, ICDAS, DIAGNOdent) included the evaluation of the appearance of the ICL before (T 0 ), 1 week after (T 1 ) treatment and at the last appointment before debonding (T 2 )., Results: Fifteen patients (8females, 7males) with 57ICL were included. Mean (SD) observation time at the last appointment before debonding was 0.5 (0.3) years. At T 0 FV and Inf did not differ significantly in ΔE (median ΔE 0,FV (25th/75th percentiles):11.6 (8.7/20.3): ΔE 0,Inf :15.1 (11.4/19.5); p T0  = 0.135), ICDAS (p T0  = 0.920) and DD (p T0  = 0.367). At T 1 and T 2 ΔE values (p T1 <0.001, p T2 <0.001), ICDAS scores (p T1 <0.001, p T2 <0.001) and DIAGNOdent values (p T1  = <0.001, p T2  = <0.001) for Inf were significantly reduced whereas ΔE values (p T1  = 0.382, p T2  = 0.072) and ICDAS scores (p T1  = 0.268, p T2 <0.001) for FV remained unchanged., Conclusions: Resin infiltration effectively masked ICL during treatment with fixed orthodontic appliances both immediately after application and at the last appointment before debonding. Furthermore, the visual appearance of fluoridated lesions was not as satisfactory as that of the infiltrated ones at both T 1 and T 2 ., Clinical Significance: Resin infiltration effectively masked ICL during treatment with fixed orthodontic appliances both immediately after application and at the last appointment before debonding. Furthermore, the visual appearance of fluoridated lesions was not as satisfactory as that of the infiltrated ones immediately after first application as well as half a year after application., Trial Registration: German Clinical Trials Register (DRKS-ID: DRKS00011797)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H.M.-L is appointed as inventor for patents of an infiltration technique for dental caries lesions, held by Charité-Universitätsmedizin Berlin, and receives royalties from DMG, the manufacturer of Icon. All other authors declare no conflicts of interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Bromelain is a potent proteolytic enzyme that has a unique functionality makes it valuable for various therapeutic purposes. This study aimed to develop three novel formulations based on bromelain to be used as chemomechanical caries removal agents., Methods: The novel agents were prepared using different concentrations of bromelain (10-40 wt. %), with and without 0.1-0.3 wt. % chloramine T or 0.5-1.5 wt. % chlorhexidine (CHX). Based on the enzymatic activity test, three formulations were selected; 30 % bromelain (F1), 30 % bromelain-0.1 % chloramine (F2) and 30 % bromelain-1.5 % CHX (F3). The assessments included molecular docking, Fourier-transform infrared spectroscopy (FTIR), viscosity and pH measurements. The efficiency of caries removal was assessed by DIAGNOdent pen, measuring the excavation time and number of applications, followed by a morphological evaluation of the remaining dentine using scanning electron microscopy (SEM). The results were compared to Brix 3000 as a control., Results: The chloramine and chlorhexidine were chemically compatible with bromelain without compromising the enzyme activity. All experimental formulations showed higher viscosity and pH in comparison to Brix 3000. The DIAGNOdent readings were <20 in all groups, and the lowest readings were observed in F2. The excavation time and number of applications were lowest in F2 and F1. Both F2 and F3 produced smooth dentine surfaces with less tissue debris, but more patent dentine tubules were observed in F1 and F2., Conclusions: The bromelain-contained formulations showed a potential to be used as chemomechanical caries removal agents in vitro. Further laboratory and clinical studies are needed to validate this claim., Clinical Significance: The bromelain from pineapple stem has broad specificity for cleavage the peptide bonds in denatured protein to facilitate their removal. The study proved the efficiency of this enzyme to remove the dental caries chemomechanically when used alone or conjugated with chloramine and/or chlorhexidine to enhance the disinfecting and cleansing properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To investigate enamel remineralization and antimicrobial effect of sodium fluoride (NaF) varnish containing calcium strontium silicate (CSR)., Methods: CSR was synthesized by sol-gel process and incorporated in 5 % NaF varnish at three different concentrations (1 %, 2 %, and 4 % w/v). The treatment/control groups were: 1 % CSR+NaF, 2 % CSR+NaF, 4 % CSR+NaF, NaF, and no treatment. Strontium and fluoride release from the varnishes was evaluated. Sound enamel specimens (n = 6) were demineralized, varnish-treated, and subjected to remineralization cycle. Mineral density of enamel specimens was evaluated using micro-CT. Antimicrobial effect of the varnishes on Streptococcus mutans and Lactobacillus acidophilus biofilms was assessed using confocal laser scanning microscopy. The HGF-1 cytotoxicity of the varnishes was examined using CCK-8 assay., Results: Both 2 % and 4 % CSR+NaF varnishes showed significantly higher F release and remineralization potential than NaF varnish (p < 0.05). Dead bacterial proportion of 4 % CSR+NaF varnish was significantly higher than NaF varnish (p < 0.05). The CFUs values of both S. mutans and L. acidophilus were significantly lower in 4 % CSR+NaF group than NaF group (p < 0.05). No significant difference in cell viability was observed among the groups (p > 0.05)., Conclusions: Incorporation of 4 % CSR in a NaF varnish significantly enhanced its enamel remineralization and antimicrobial potential with no cytotoxic effect., Clinical Significance: Dental caries is a major public health problem globally. The study highlights the great potential of CSR-doped NaF varnish as a novel anti-caries agent with synergistic remineralizing and antimicrobial properties to combat early enamel caries lesions in the general population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Answer the PICO question: Do class I and II posterior restorations in permanent teeth placed with high-viscosity glass-ionomer cement (HV-GIC) fail more than composite resin (CR) restorations?, Data: The study was registered in the PROSPERO database (CRD42020138290). Randomized and controlled clinical trials, comparing the performance of HV-GIC and CR in load bearing cavities of posterior permanent teeth were included. Cochrane risk of bias tool and GRADE were used to assess the quality and certainty of the evidence. Meta-analyses were performed for clinical outcomes on USPHS and FDI criteria for 12-, 24- and 36-months follow-ups., Sources: PubMed, Scopus and Web of Science were last searched on April 2, 2022, without language or date restrictions. Reference lists of primary studies and their related article link in PubMed were manually searched., Study Selection: Ten studies were included, while data from 8 were used for the meta-analyses. A total of 849 HV-GIC and 800 CR restorations were followed. The primary outcome was the fracture/retention of the restoration, with a comparable performance for both materials on all follow-ups. The 36 months follow-up for class I restorations (longest) showed risk difference of -0,00 (95%CI -0,03 to 0,03; p = 0,98) and no heterogeneity (p = 0,98, I 2 =0%). The certainty of the evidence is moderate, as all included studies were at an uncertain risk of bias., Conclusions: HV-GIC and CR presented comparable clinical performance in posterior permanent teeth up to 36 months. HV-GIV wear in class I restorations followed by 24 months was the only poorer result compared to CR., Clinical Significance: Conservative load bearing cavities in permanent posterior teeth can be restored with HV-GIC with comparable clinical performance to CR expected at least up to 3 years. HV-GIC is a valuable direct restorative option for posterior teeth in high caries risk patients, in which CR is frequently associated with failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: This in vitro study investigated the ability of a blue protein-based hydroxyapatite porosity probe to selectively detect artificial enamel caries-like lesions of varying severities., Methods: Artificial caries-like lesions were formed in enamel specimens using a hydroxyethylcellulose-containing lactic acid gel for 4/12/24/72 or 168 h. One untreated group was used as a control. The probe was applied for 2 min and unbound probe rinsed off with deionized water. Surface color changes were determined spectrophotometrically (L*a*b* color space) and with digital photography. Lesions were characterized using quantitative light-induced fluorescence (QLF), Vickers surface microhardness, and transverse microradiography (TMR). Data were analyzed using one-way ANOVA., Results: Digital photography did not reveal any discoloration in unaffected enamel. However, all lesions stained blue with color intensity positively correlated with demineralization times. The color data reflected similar trends: lesions became significantly darker (L* decreased) and bluer (b* decreased), while overall color differences (ΔE) increased significantly after probe application (4-h lesion, mean±standard deviation: ΔL*=-2.6 ± 4.1/Δb*=0.1 ± 0.8/ΔE=5.5 ± 1.3 vs. 168-h lesion: ΔL*=-17.3 ± 1.1/Δb*=-6.0 ± 0.6/ΔE=18.7 ± 1.1). TMR analysis revealed distinct differences in integrated mineral loss (ΔZ) and lesion depth (L) between demineralization times (4-h lesion: ΔZ=391±190 vol%min × µm/L = 18.1 ± 10.9 µm vs. 168-h lesion: ΔZ=3606±499 vol%min × µm/L = 111.9 ± 13.9 µm). QLF and microhardness were also able to differentiate between demineralization times. L and ΔZ strongly correlated (Pearson correlation coefficient [r]) with Δb* (L vs. Δb*: r=-0.90/ΔZ vs. Δb*: r=-0.90), ΔE (r = 0.85/r = 0.81), and ΔL* (r=-0.79/r=-0.73)., Conclusion: Considering the limitations of this study, the blue protein-based hydroxyapatite-binding porosity probe appears to be sufficiently sensitive to distinguish between unaffected enamel and artificial caries-like lesions., Clinical Significance: Early detection of enamel caries lesions remains one of the most critical aspects in the diagnosis and management of dental caries. This study highlighted the potential of a novel porosity probe in detecting artificial caries-like demineralization by objective means., Competing Interests: Declaration of Competing Interest This work was support by Incisive Technologies Pty Ltd, Melbourne, Victoria, Australia. JEM and KAH are employees of and have equity in Incisive Technologies., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effect of different toothpastes either containing 5,000ppm-F, 1,450ppm-F or bioactive glass (BG) with 540ppm-F on artificial root carious lesions (ARCLs)., Method: The crowns of 23 extracted sound teeth were removed leaving their roots only. Subsequently, each root was divided into four parts. A total of 15 sound root dentine (SRD) was left untreated as baseline. The ARCLs were developed for the remaining roots using demineralisation solution (pH-4.8). 15-ARCLs samples were then left untreated. The rest of samples were divided into four groups (n = 15 each) and treated with Group-1(BG with 540ppm-F); Group-2(5000ppm-F); Group-3(1450ppm-F) and Group-4(deionised water). 13-day pH-cycling included using demineralisation solution for 6 h, then placing samples into remineralisation solution (pH-7) for 16 h. Each sample was brushed with the assigned toothpaste twice a day during pH-cycling. Fluoride concentrations at each time point were measured using F-ISE, whilst calcium (Ca 2+ ) and phosphorus (P) ion release was determined using ICP-OES, KHN, XRD, 19 F-MAS-NMR analyses., Results: KHN showed significant surface changes for each group (p<0.001). The uptake of Ca 2+ occurred at days 1-2, phosphorus ion loss was high when compared to the uptake in all groups. XRD showed presence of sharp diffraction lines evidencing apatite formation for Groups 1-3. 19 F-MAS-NMR confirmed fluorapatite presence in Groups 1-3., Conclusion: All toothpastes were promising in fluorapatite formation. BG with 540ppm-F toothpaste released more ions (Ca 2+ and P) and reharden the artificial root carious lesions when compared to other groups. However, 1450ppm-F toothpaste showed more fluoride-substituted apatite formation whilst 5000ppm-F toothpaste had more fluorapatite formation., Clinical Significance: Toothpaste containing BG with 540ppm-F, 5000ppm-F and 1450ppm-F toothpastes are likely to have a significant impact in reversing and arresting root caries. However, randomised controlled double-blinded clinical trials are required to translate these results into clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H. Chen and A. Baysan declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. R. Hill has small number of shares in Biomin Technologies Ltd., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Caries treatment with silver diamine fluoride (SDF) is effective, but often leads to irreversible tooth discoloration. This study aimed to investigate older patients' perceptions of root caries treatment with SDF and to identify factors that influence their decision process., Methods: Fifteen interviews were conducted in older patients (mean, min/max: 83, 71/92 years) with root caries experience, following a semi-structured interview-guide based on the domains of the Theoretical Domains Framework (TDF) including three case vignettes of SDF treatment. Transcripts of the interviews were used to perform deductive and inductive content analysis along the TDF and Capability-Opportunity-Motivation-Behavior model (COM-B) to assess influential factors., Results: All TDF domains and behavior determinants of the COM-B were covered, identifying twenty-two barriers, facilitators and conflicting themes. Main barriers for consenting to SDF treatment were patients' perceptions of permanent staining of visible root caries lesions, as well as preconceptions about those of others and lack of knowledge about root caries and SDF. Main facilitators were trust in advice given by dentists, especially regarding new treatment options, that aesthetics were less important in non-visible areas and the importance of tooth preservation and feasibility of treatments when immobile or in need of care., Conclusion: Permanent discoloration is an important barrier to older patients' acceptance of SDF treatment for visible root caries. However, patients appear to accept SDF treatment under certain conditions, including less visible lesions or in comparison to more invasive treatment options., Clinical Significance: Our findings contribute to understanding both barriers and facilitators when treating root caries in older patients with SDF., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Objective(s): The objectives of the present study were to examine the - a) enamel remineralization potential of synbiotic-fluoride (SF) therapy using a multi-species bacterial pH-cycling model; and b) cytotoxic and genotoxic effects of SF therapy extracts., Materials and Methods: The SF therapy group comprised of 2% arginine (Arg), 0.2% NaF, and a probiotic Lactobacillus rhamnosus GG (LRG). The intervention groups studied were: 1) No treatment; 2) 2% Arg; 3) 0.2% NaF; 4) LRG; 5) 2% Arg+0.2% NaF; 6) 2% Arg+LRG; 7) 0.2% NaF+LRG; and 8) 2% Arg+0.2% NaF+LRG (SF therapy). The enamel remineralization potential of SF therapy was investigated under cariogenic biofilm challenge; while the cytotoxicity and genotoxicity of SF therapy extracts were examined on HGF-1 and Chinese hamster fibroblast V79, respectively. To determine the remineralization effect, the specimens were subjected to mineral density (MD) assessment using micro-CT, Ca/P molar ratio with SEM-EDX, and enamel fluoride uptake (EFU) estimates. The HGF-1 proliferation assessment was quantified using MTT/CCK-8 assays with qualitative analysis by nuclei staining Hoechst-based fluorescence imaging. The genotoxicity was determined by micronuclei formation test., Results: Mineral gain and %remineralization derived from MD assessment for the SF therapy were significantly higher than the other groups (p<0.05). The %ΔCa/P for the SF and 2% Arg+0.2% NaF were significantly higher than the other groups (p<0.05). The SF and 2% Arg+0.2% NaF groups had the highest EFU compared to the other groups (p<0.05). No significant difference in the %viable HGF-1 cells were observed between the treatment interventions and no treatment group (p>0.05). Compared to the EMS-positive control, the micronuclei formation for all the intervention groups was significantly lower (p<0.05), with no significant difference among the treatment groups (p>0.05)., Conclusion: The SF therapy enhanced enamel remineralization with no biocompatibility concerns., Clinical Significance: With the enhanced enamel remineralization potential discerned in the present study, the SF therapy can be used as a promising caries-preventive agent targeted for high caries-risk individuals., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To evaluate and compare the clinical performance and cost effectiveness of Silver Modified Atraumatic Restorative Treatment (SMART) and Atraumatic Restorative Treatment (ART) restorations in primary molars over 12 months follow up period., Materials and Methods: Sixty-seven children, aged 5-9 years old having at least one asymptomatic primary molar with active caries, were randomly assigned to either the test arm (SMART) or the control arm (ART). Clinical performance was assessed after 6 and 12-months using the modified United States Public Health Services criteria. The trial was registered at Clinical Trial.gov with a registration number (NCT03881020). Treatment time for each restoration was recorded, Kaplan-Meier survival analysis and the log-rank test were performed (p<0.05) and cost effectiveness was measured at the end of the study., Results: Both techniques showed comparable clinical performance and the mean survival time was 11.8 and 11.6 months for SMART and ART restorations respectively with no detected significant differences (p=0.416). Mean treatment time for SMART restorations (7.8 min.), however, was significantly lower than ART (15 min.) (p < 0.001). SMART technique, also, showed statistically significant lower mean total cost per restoration (p <0.001)., Conclusions: Though SMART and ART have comparable clinical performance and survival in single-surface occlusal restorations in primary molars, SMART is less time consuming and more cost effective., Clinical Significance: Using SMART technique could change paradigms in caries management. Being a patient friendly and cost-effective approach, it could be adopted as a superior treatment option when dealing with young children, those with behavioral and medical challenges and for promoting access to oral care among the underprivileged., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To study the effects of a 445 nm diode laser (L) and silver diamine fluoride (F) on preventing enamel demineralisation and inhibiting cariogenic bacteria., Methods: Thirty-three enamel slices were sectioned each into four blocks for four groups to receive L with F (LF), F, L and Water (W, control). Ten blocks from each group were used to evaluate demineralisation. Surface morphology, lesion depth and nanohardness of the blocks after pH-cycling were studied by scanning electron microscopy (SEM), nanohardness test, and micro-computed tomography, respectively. Twenty-three blocks per group were used for biofilm assessment. Morphology, viability, and growth kinetics of the Streptococcus mutans biofilm were assessed by SEM, confocal laser scanning microscopy, and the counting of colony-forming units (CFUs), respectively., Results: SEM images of LF-treated enamel showed an intact surface compared with other groups. Nanohardness (GPa) for LF, F, L and W were 1.43±0.17, 1.01±0.11, 1.04±0.13 and 0.73±0.14, respectively (p &lt; 0.001; LF&gt;F, L&gt;W). Their lesion depths (µm) were 46±8, 52±6, 88±13 and 111±9, respectively (p &lt; 0.001; LF, F&lt;L&lt;W). SEM showed few bacteria for LF and F compared with other groups. Their dead-live ratio were 1.67±0.13, 1.60±0.15, 0.39±0.05 and 0.32±0.05, respectively (p &lt; 0.001; LF, F&gt;L&gt;W). Log CFUs for LF, F, L and W were 4.2±0.3, 4.5±0.2, 7.9±0.3 and 9.4±0.2, respectively (p &lt; 0.05; LF&lt;F&lt;L&lt;W). Two-way ANOVA analysis revealed an interaction effect on nanohardness and Log CFUs between the laser irradiation and SDF treatment (p &lt; 0.001)., Conclusion: This study showed a superior caries preventive effect of a combined treatment of the diode laser and SDF. Because diode laser and SDF are affordable and readily available, clinicians can provide this treatment to their patients for caries prevention., Clinical Significance Statement: Diode lasers are handy, afforable and readily avaliable to clinicians. This study provides information of use of 445 nm diode laser for caries prevetion. The laser irradiation hopefully can be added before conventional topical SDF application., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effectiveness of glass ionomer cement (GIC) restorations on preventing new caries in primary or permanent dentitions compared with other types of restorations., Data: Randomized controlled clinical trials evaluating caries experience increment or caries incidence in patients with GIC restorations, including conventional GIC (CGIC) and resin-modified GIC (RMGIC) restorations, were included., Sources: A systematic search of publications in English was conducted in PubMed/Medline, Web of Science, Cochrane, and Scopus databases., Study Selection/results: This review included 10 studies reporting caries preventive effect of GIC restorations and selected 5 studies for meta-analysis. Patients with GIC restorations showed lower caries incidence compared with other restorations in primary and permanent dentition [RR=0.67, 95% CI:0.55-0.82, p < 0.0001]. Patients with CGIC restorations showed lower caries incidence compared with amalgam restorations [RR=0.57, 95% CI:0.43-0.76, p = 0.0001] and RMGIC restorations [RR=0.70, 95% CI:0.56-0.87, p = 0.002], but no statistical difference with composite resin restorations [RR=0.73, 95% CI:0.51-1.04, p = 0.08] in primary dentition. Patients with RMGIC restorations showed no statistical differences of caries incidence compared with composite resin restorations in primary and permanent dentition [RR=0.83, 95% CI:0.56-1.22, p = 0.33]., Conclusions: GIC restorations presented a better preventive effect on new caries than other restorations did in primary and permanent dentitions. CGIC restorations presented a better caries preventive effect on new caries than RMGIC and amalgam restorations in primary dentitions did. RMGIC restorations showed similar preventing effect on new caries with composite resin restorations in primary and permanent dentitions., Clinical Significance: This review affirmed the potential of GIC in preventing new caries development in the dentition., Competing Interests: Declaration of Competing Interest The authors state that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To assess the clinical evidence for professionally applied fluoride therapy to prevent and arrest caries in older adults., Data/sources: Two independent researchers searched the English literature published up to 31st Dec 2021 in five databases (PubMed, Scopus, the Cochrane Library, EMBASE, and Web of Science) for clinical trials with a comparison group on professionally applied fluoride therapy for caries prevention or arrest at older adults aged ≥60 years with any follow-up period. The outcomes were the mean difference in the number of new caries/caries-prevented fraction and caries arrest rate. The Cochrane guidelines were used for the risk of bias assessment., Study Selection/results: Five hundred and twenty-seven studies were identified, and seven studies were finally included. Five studies were rated as having 'low risk'. The root caries-prevented fraction of 38% silver diamine fluoride (SDF) solution, 5% sodium fluoride (NaF) varnish, and 1.23% acidulated phosphate fluoride (APF) gel were 25-71%, 64%, and 32%, respectively. Meta-analysis indicated a decrease in the number of new root caries by 0.55 (95% CI: 0.32-0.78; p < 0.001) and an overall proportion of arrested root caries of 42% (95% CI: 33% to 49%; p < 0.001) after receiving 38% SDF application at the 24-month follow-up., Conclusions: According to the findings, 5% NaF varnish and 1.23% APF gel prevented root caries, whereas 38% SDF solution prevented and arrested root caries in older adults. More well-designed clinical trials should be conducted to investigate various methods in caries prevention and arrest in older adults., Clinical Significance: Preventive measures effective in other age groups may not suit older adults, as caries type and associated risk factors vary. To date, no systematic review has evaluated professionally applied fluoride therapy in older adults. Evidence from clinical trials in older adults could aid clinical practice and public health measures. The International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42022307025., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: This study aimed to explore parental perspectives on an outreach dental service and silver diamine fluoride (SDF) therapy to arrest and prevent early childhood caries., Methods: This qualitative study collaborated with an outreach service offering SDF therapy to kindergarten children and oral health education to the children's parents. The study was conducted in 2018 using purposive sampling of participating parents from selected kindergartens in Hong Kong until data saturation was reached. Five parents were recruited from each kindergarten for a focus-group discussion. The data were manually coded for thematic analysis., Results: Ten focus-group discussions with 49 parents were held to achieve data saturation. The oral health education largely met the parents' expectations regarding enriching their child's oral health knowledge, raising their child's dental awareness, and promoting parent-assisted toothbrushing. Some parents did not consent to their children undergoing SDF therapy because it permanently stains caries black, which adversely affects appearance. They were also concerned about potential toxicity of SDF. Parents who did consent preferred the arrest and prevention of dental caries over aesthetics which are temporary until the primary teeth exfoliate., Conclusions: This outreach dental service improved parental dental knowledge. Some parents were generally satisfied with the outreach dental services, preferred caries arrest over aesthetics, and accepted SDF therapy. However, some parents worried about SDF toxicity. The results of this study provide rich, in-depth, and multi-dimensional information about parents' experiences of taking the outreach dental service and their opinions about SDF therapy., Clinical Significance: Dentists can use the arguments from this study to form a protocol for communicating with parents before SDF therapy. This study shows that outreach dental services improve dental knowledge. Some parents prefer caries arrest over aesthetics and accept SDF therapy; however, some parents worry about SDF toxicity., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: The aim of this RCT was to compare the caries preventive efficacy and the slowing down of previous caries lesions of toothpastes containing fluoride biomimetic hydroxyapatite (HA) complex compared to sodium monofluorophosphate fluoridated toothpastes in Italian schoolchildren. To validate this hypothesis a triple-blind randomized clinical trial was designed., Methods: In total 610 children (4-5 and 6-7 years) were enrolled. Four toothpastes, two containing fluoride-substituted hydroxyapatite (HAF) (1000 and 1450 ppmF) and magnesium-, strontium-, carbonate-substituted hydroxyapatite, in a chitosan matrix and two Mono fluoridated toothpastes (1000 and 1450 ppmF) were randomly administered during 24 months to two groups with younger children (G young ) and to two groups with older children (G old ), those containing 1450 ppmF. ICDAS was used to score lesions as initial (up to score 2), moderate (scores 3-4) and severe (scores 5-6). The children were instructed to brush for two minutes three times/day. Caries examination was repeated at 12 and 24 months. The efficacy of the treatment was assessed by calculating the reduction in Risk Ratio (RR) and the number needed to treat (NNT). Results; Overall, 518 patients (G young  = 268; G old  = 250) concluded the trial. The drop-rate was 11.84% for G young and 17.22% for G old . The caries increment at 24-month evaluation was statistically lower in the primary dentition in the HAF arms compared to the traditional fluoridated arms (0.18 vs 0.27 p = 0.04 in G young and 0.16 vs 0.30 p = 0.01 in G old for severe lesions). In the permanent dentition (G old ), caries increase was also statistically lower in the HAF arm, both for initial and severe lesions (0.09 vs 0.17 p = 0.02 and 0.18 vs 0.28 p = 0.01, respectively). In primary dentition, children receiving HAF Toothpaste had a RR of 39% (G young ) and 38% (G old ), compared to children receiving traditional Toothpastes. The RR in the permanent dentition was 29% in children treated with HAF toothpaste. Conclusions; The use of toothpastes containing biomimetic hydroxyapatite and fluoride reduces caries increment in children over a period of 2 years more than traditional fluoridated toothpastes., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: This study aims to review systematically the dental pulp response to silver diamine fluoride (SDF) treatment, including the inflammatory response, pulp cells activity, dentinogenesis, silver penetration, and the presence of the bacteria in the dental pulp., Data: In vitro studies, animal studies, clinical studies, and case reports on the use of SDF on vital dental pulp were included. Quality assessment of the included studies was conducted. A narrative synthesis of the collected data was performed., Sources: A systematic search was performed in ProQuest, PubMed, SCOPUS, and Web of Science databases for articles published from inception to Nov 1, 2021., Study Selection: The initial search identified 1,433 publications, of which five publications met the inclusion criteria. These five publications reported the effect of direct/ indirect SDF application on the vital pulp of a total of 30 teeth. Direct SDF application on vital pulp caused pulp necrosis. Indirect SDF application caused none or mild inflammatory response of dental pulp. The odontoblasts in the dental pulp showed increased cellular activity. Tertiary dentine was formed in the pulpal side of the cavity with indirect SDF application. Accentuated incremental lines of tertiary dentine reflected disturbances in mineralisation. Silver ions were found to penetrate along the dentinal tubules but were not detected inside the pulp., Conclusion: According to the limited available literature, direct SDF application causes pulp necrosis. Indirect SDF application is generally biocompatible to dental pulp tissue with a mild inflammatory response, increased odontoblastic activity, and increased tertiary dentine formation. Future studies with precise quantitative and qualitative tests, larger sample size and longer follow-up time are imperative to understand the biological activity of dental pulp to SDF treatment., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the remineralizing effect of varnishes containing different concentrations of S-PRG filler or sodium fluoride on enamel caries lesions., Methods: Enamel specimens were obtained from bovine incisors, flattened and polished. Half of the surface was protected, and artificial caries lesion was created in the unprotected area. They were assigned into six groups (n=20) according to the varnish applied: four containing S-PRG filler with different concentrations (10%, 20%, 30% and 40% w/w), one containing 5% sodium fluoride (5%NaF) as positive control, and one without treatment as a negative control (NC). Varnishes were applied on specimen's caries-affected surface and removed after 24 h. Varnish application and pH cycling (8 days) were performed twice. Cross-sectional microhardness was measured (10-100 µm depth). Knoop microhardness percentage (KHN%) of caries affected/treated area in relation to the sound enamel area at the same depth was calculated. The area under the curve (AUC) and the Δ AUC were also calculated. Statistical analysis was performed by two-way ANOVA for KHN% and one-way ANOVA for Δ AUC , followed by Tukey test (α=5%)., Results: Significant differences were found for the factors "treatment" (p=0.0001) and "depth" (p=0001). For the factor "treatment", the results of the Tukey test were: NC-62.2(10.3)a, 10%S-PRG-69.2(9.3)b, 20%S-PRG-71.8(9.7)bc, 30%S-PRG-74.5(9.4)c, 5%NaF-79.6(8.7)d, 40%S-PRG-85.6(8.4)e. In relation to Δ AUC , significant differences were observed among the groups (p=0.0001) and better results for 40% S-PRG and 5%NaF., Conclusions: The varnish containing 40% S-PRG fillers was the most effective to promote the enamel caries remineralization, followed by the one containing 5% sodium fluoride., Clinical Significance: The varnish containing 40% of S-PRG fillers represents an alternative for initial enamel caries remineralization, since it was more effective than the conventional 5% NaF based product., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To summarize the evidence on prevention of early childhood caries (ECC) by professionally or self-applied topical fluorides using network meta-analysis., Data: Randomized-controlled trials with minimum 1-year follow-up assessing caries-preventive effect among children younger than six years., Sources: Eight electronic databases and grey literature., Study Selection: After screening and data extraction, risk of bias assessment using Cochrane risk of bias tool 2.0 was done. Twenty-four trials were included, among which 17 were assessed as "high risk" and remaining as "low risk". Fifteen studies evaluated professionally-applied, and the other nine used self-applied topical fluorides. Ten studies on professionally-applied fluorides reporting the net caries increment (dmfs increment) at 2-years follow-up were included in Network meta-analysis (NMA). NMA and ranking the interventions were conducted using a frequentist random-effects approach and surface under the cumulative ranking command, followed by assessing the certainty of evidence using an extension of GRADE approach with CINeMA framework. Among the eight included interventions of professionally-applied fluorides, only two, i.e., 3-monthly 0.9% difluorosilane (DFS) and 6-monthly 5% sodium fluoride varnish were effective in preventing ECC compared to control with 3-monthly DFS application ranking higher than 6-monthly sodium fluoride varnish application., Conclusion: Among all the professionally-applied topical fluoride interventions reviewed, very low to moderate evidence was found with 0.9% DFS application at 3-monthly intervals, which was ranked highest in prevention of ECC. Among the included studies on self-applied topical fluorides, the evidence was inconclusive due to heterogeneity among studies., Clinical Significance: The 0.9% DFS varnish applied every 3 months is most effective for preventing early childhood caries. The review recommends that good quality studies be conducted in future, comparing two or more interventions for both self- as well as professionally-applied topical fluoride agents with adequate follow-up., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: The oral biofilm structure or composition can affect the penetration of remineralizing agents. Therefore, this study evaluated the remineralizing efficacy of fluoride using a pH-cycling model with oral microcosm biofilms., Methods: Artificial carious lesions were formed in 80 bovine incisors. The pH-cycling conditions with or without oral microcosm biofilms were applied to 40 specimens each. The pH-cycling scheme was repeated for 12 days. Fluorescence loss (ΔF,%) of early carious lesions was measured for all specimens using a quantitative light-induced fluorescence-digital camera, before and after fluoride application. Biofilms on specimens were further analyzed for red fluorescence intensity (red/green ratios) and colony-forming unit counts. The effects of pH-cycling conditions and treatments on changes in ΔF (ΔΔF) and the effects of interactions between factors were analyzed using two-way analysis of variance., Results: The fluoride-treated group with oral biofilms had an approximately 0.89-fold lower ΔΔF than the fluoride-treated group without oral biofilms (p < 0.0001). When oral biofilms were absent, the fluoride-treated group showed a 1.31-fold greater ΔΔF compared to that in the distilled water-treated group (p < 0.0001). When oral biofilms were present, the fluoride-treated group showed a 1.14-fold greater ΔΔF compared to that in the distilled water-treated group; however, this difference was not statistically significant., Conclusions: There was a significant difference in fluoride remineralizing efficacy based on the presence of biofilms on early carious lesions. Therefore, fluoride remineralization assessment in the absence of oral biofilms could lead to an overestimation of efficacy., Clinical Significance: Fluoride application might not have a robust remineralization effect on early carious lesions in the presence of a mature biofilm on the tooth surface., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: The aim of this randomized, double-blind, two-arm crossover in situ study was to investigate whether nano-hydroxyapatite (nanoHAP) dental lotion (Apagard Deep Care) applied immediately after tooth-brushing with nanoHAP toothpaste (Apagard M-plus) enhances the remineralization promotion and the demineralization inhibition efficacies of nanoHAP toothpastes., Methods: 64 sound enamel blocks and 64 blocks bearing artificially-produced initial caries were produced from human permanent molar teeth. During each treatment period, lasting 14 days per arm, two blocks, one sound and one lesion-bearing, were exposed to either 5% nanoHAP-containing or placebo dental lotion after tooth-brushing with 5% nanoHAP toothpaste, via an intra-oral appliance worn by 30 adults in each of the study groups. Baseline and post-test mineral loss were quantified using transverse microradiography (TMR). One-sided t-test of one group mean was used for intragroup comparison, while two-sided t-test of two independent means was used to compare the two dental lotions., Results: Pairwise comparison (baseline vs. post-test) indicated significant (p<.001) remineralization by nanoHAP toothpaste in both groups. However, when compared against each other, there was a significantly (p<.001) greater percentage of remineralization with nanoHAP lotion [58.4(±1.8)%] than with placebo lotion [37.7(±2.2)%]. TMR examination showed absolute demineralization inhibition in sound enamel blocks exposed to either lotions., Conclusions: Toothpaste containing 5% nanoHAP effectively remineralized initial caries and inhibited demineralization of healthy enamel; however, the application of a dental lotion containing 5% nanoHAP after brushing resulted in superior remineralization compared to a placebo lotion., Clinical Significance: Dental lotion containing 5% nanohydroxyapatite used immediately after toothbrushing with 5% nanohydroxyapatite toothpaste can serve as an adjunct to enhance the clinical benefits of the toothpaste., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To develop a novel dual-action peptide with antimicrobial and mineralising properties., Methods: A novel peptide, namely GA-KR12, was synthesised through grafting gallic acid to KR12. The secondary structure of GA-KR12 was evaluated by circular dichroism spectroscopy. The stability was evaluated by high-performance liquid chromatography. The cytotoxicity was evaluated by a mitochondrial dehydrogenase activity assay. The antimicrobial properties against common cariogenic species were evaluated by minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). The morphology of cariogenic species was analysed by transmission electron microscope (TEM). To assess the mineralising effect of GA-KR12 on enamel, the lesion depths, mineral loss, surface morphology, calcium-to-phosphorus ratio and crystal characteristics were determined using micro-computed tomography, scanning electron microscopy (SEM) and energy dispersive spectroscopy X-ray diffraction, respectively., Results: GA-KR12 did not exhibit cytotoxicity against HGF. Around 82% of the GA-KR12 remained in human saliva at 37°C for 1 h. The MIC and MBC/MFC against the tested species were 10-320 μM and 20-1,280 μM, respectively. GA-KR12 induced remarkable morphological defects in the tested species. The enamel treated with GA-KR12 had smaller lesion depths (p < 0.001), less mineral loss (p < 0.001) and higher calcium-to-phosphorus molar ratios (p < 0.001) than those in the enamel treated with water. SEM showed a well-organised prism pattern in enamel treated with GA-KR12. X-ray diffraction revealed that the hydroxyapatite on the enamel treated with GA-KR12 was better crystalised., Conclusions: This study developed a biocompatible and stable peptide which inhibited the growth of cariogenic species and mineralised the enamel caries., Clinical Significance: The novel dual-action peptide, GA-KR12, is potential applicable in the management of caries., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To investigate the antibacterial and remineralising effects of a novel dual-action antimicrobial peptide, GA-KR12, on artificial dentine caries., Methods: Human dentine blocks with artificial carious lesions were allocated to two groups - Group 1: dentine blocks treated with the novel antimicrobial peptide GA-KR12 twice daily; Group 2: dentine blocks received water as the negative control. Two groups underwent Streptococcus mutan biofilm-remineralisation cycles at 37 °C for 7 days. The morphology, viability and growth kinetics of the S. mutans biofilm were evaluated by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and colony-forming unit (CFU) counting, respectively. The dentine blocks' lesion depths and mineral loss, changes in chemical structure, dentine surface morphology and crystal characteristics were determined using micro-computed tomography, Fourier transform infrared (FTIR), SEM and X-ray diffraction (XRD), respectively., Results: The surface of the dentine blocks in Group 1 was partially covered by S. mutans with damaged cell structure. Group 2 showed affluent growth of S. mutans covering the dentine surface when compared to Group 1. The dead-to-live ratio of Group 1 and Group 2 were 0.78 ± 0.01 and 0.47 ± 0.08, respectively (p < 0.001). The Log CFUs of Group 1 and Group 2 were 7.14 ± 0.30 and 8.24 ± 0.20, respectively (p < 0.001). The lesion depths of Group 1 and Group 2 were 109 ± 1 µm and 135 ± 3 µm, respectively (p < 0.001). The mineral loss of Group 1 and Group 2 were 0.59 ± 0.08 gHApcm -3 and 0.81 ± 0.07 gHApcm -3 , respectively (p < 0.001). FTIR showed the amide I-to-hydrogen phosphate (HPO 4 2- ) ratios of Group 1 and Group 2 were 0.25 ± 0.05 and 0.39 ± 0.05 (p < 0.001), respectively. SEM images showed Group 1 had less exposed dentine collagen fibres than Group 2. The XRD revealed that the hydroxyapatite in Group 1 was well crystalised., Conclusion: This study demonstrated that the novel antimicrobial peptide GA-KR12 inhibited the growth of S. mutans biofilm and enhanced the remineralisation of artificial dentine caries., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To investigate the remineralizing effect of a strontium-doped bioactive glass (HX-BGC) and fluoride on demineralized enamel and dentine., Materials: Sixty demineralized human tooth specimens were allocated to four groups. Group 1 received 5% HX-BGC, Group 2 received 5% HX-BGC and 1450 ppm fluoride, Group 3 received 1450 ppm fluoride, and Group 4 received deionized water as negative control. The specimens were subjected to pH cycling for 14 days. The surface morphology, lesion depths, crystal characteristics and collagen matrix degradation of the specimens were assessed by scanning electron microscopy (SEM), micro-computed tomography (mico-CT), X-ray diffraction (XRD), and spectrophotometry with a hydroxyproline (HYP) assay, respectively., Results: SEM images showed the enamel surface was smooth with regularly arranged enamel rods in Groups 1-3. Granular grains were observed in both inter-tubular and intra-tubular dentine in Groups 1-3. The mean lesion depths in enamel were 80.8 μm, 50.6 μm, 72.7 μm and 130.7 μm in Groups 1-4, respectively (p < 0.001), and those in dentine were 152.6 μm, 140.9 μm, 165.4 μm and 214.1 μm, respectively (p < 0.001). The differences in mean mineral loss in enamel and in dentine between the four study groups follow the same pattern as that of the differences in lesion depth. XRD illustrated apatite formation in each group. There were no significant differences in the HYP concentrations among the four groups (p = 0.261)., Conclusion: Combined use of HX-BGC and fluoride can reduce mineral loss and promote remineralization of demineralized enamel and dentine through the precipitation of newly formed apatite., Clinical Significance: Adjunctive use of HX-BGC may enhance the remineralization effect of fluoride in the management of early dental caries lesions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Silver diammine fluoride (SDF) is a caries-arresting agent for dentine lesions. This study investigated the effect of application frequency of SDF when used with glass ionomer cement (GI) for remineralising carious dentine., Methods: Freshly extracted human posterior teeth with advanced caries were used. After superficial removal of infected dentine, single (G3), double (G4), triple (G5) applications of SDF (Advantage Arrest SDF 38 %) followed by a layer of GI (GC Fuji IX GP) were compared to no treatment (negative control-G2), and GI only (G1). All teeth were stored in artificial saliva between treatments and for 2-weeks after final treatment. Micro-computed X-ray tomography (NSI) scans were obtained at each stage and analysed to plot mineral density-depth profile, lesion depth (LD) and mineral loss (ΔZ). Data was statistically analysed at a significance level of 0.05., Results: Mean LD values were 837 μm, 735 μm, 841 μm, 1008 μm, 707 μm at baseline and 785 μm, 727 μm, 712 μm, 855 μm, 639 μm after treatment for groups G1 to G5, respectively. Mean ΔZ values were 6327 vol%μm, 5995 vol%μm, 10014 vol%μm, 7192 vol%μm, 5649 vol%μm at baseline and 3686 vol%μm, 5126 vol%μm, 5539 vol%μm, 2327 vol%μm, 3218 vol%μm after treatment for groups G1 to G5, respectively. Paired t-test showed that LD and ΔZ changed significantly within all groups from baseline to treatment weeks following storage (p < 0.05) except LD in the control (p > 0.05). ANCOVA showed significant difference among groups in net lesion depth recovery and net mineral gain (p < 0.05), and G3 and G4 showed the highest mineral gains., Conclusion: One or two applications of SDF prior to placement of GI, were effective in remineralising advanced dentine lesions, while additional applications, when combined with GI, did not demonstrate additional benefit in this study., Clinical Significance: This short-term laboratory research study showed that one or two applications of SDF followed by GI coverage could remineralise advanced dentine caries in the presence of artificial saliva. This procedure carries potential in the treatment of difficult lesions where conventional restorations would require significant tooth structure removal through traumatic procedures., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The dysbiotic oral microbiome plays a key role in the pathogenesis of caries in children. Topical application of casein phosphopeptide-amorphous calcium phosphate containing fluoride (CPP-ACP/F) is an effective treatment modality for children with caries (CC). Hitherto the mechanism by which CPP-ACP/F modules the oral microbiome in CC has not been investigated. The study aimed to examine the CPP-ACP/F effect on the dental plaque microbiome of children group with caries., Methods: This preliminary prospective clinical cohort included 10 children with caries. The children received topical fluoride CPP-ACP/F once-a-week for one month. Plaque samples were collected before and after treatment and subjected to 16S rDNA-based next-generation-sequencing. Microbial composition, diversity and functional roles were analyzed in comparison to the clinical characteristics of cohort using standard bioinformatics tools., Results: CPP-ACP/F treatment modulated dysbiotic oral microbiome towards healthier community as the higher proportion of Proteobacteria and certain microbial protective species were enriched following CPP-ACP/F treatment. Despite overall uniformity of community structure in children with caries between the groups, some bacterial species were differentially represented in a statistically significant manner between pre- and post- treatments. Three bacterial species were found to be predictive of strongly sensitive to the CPP-ACP/F treatment, marked by decreased abundance of Lautropia mirabalis and increased abundance of Gemella haemolysans and Schwartzia succinivorans., Conclusion: Within the limits of the current study, it could be concluded that the CPP-ACP/F varnish treatment modulated the microbial composition of the dental plaque microbiome towards symbiosis. These symbiotic changes may demonstrate the potential clinical significance of CPP-ACP/F varnish treatment., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: This in vivo study compared the antibacterial effect of a self-etch adhesive with and without the brominated monomer 12-methacryloyloxydodecyl-pyridinium bromide (MDPB) on carious dentin after selective caries removal., Methods: 10 patients showing deep primary carious lesions at two posterior teeth without pulpal symptoms were included. At visit I, carious tissue was selectively removed and carious dentin was sampled with a sterile roundbur (Komet No. 18). One cavity was restored with composite (SDR, Ceram X; DENTSPLY DeTrey) using an MDPB-containing self-etch adhesive (Clearfil Protect Bond, Kuraray Noritake; PB). The other restoration served as a control (Clearfil SE Bond II, Kuraray Noritake; SE). At visit II after 8 weeks, carious dentin was sampled again. Bacterial growth in carious dentin was differentiated using microbial cultivation. Bacterial DNA from intact cells and cell-free DNA were quantified using 16S rRNA gene-based real-time PCR and the microbial community composition was analyzed by amplicon deep-sequencing. Wilcoxon test was applied for statistical analysis., Results: Both treatments showed a decrease of intact bacterial cells in carious dentin at visit II compared to visit I (PB: visit I: 1.1*10 6 , visit II: 1.7*10 5 (p = 0.03); SE: visit I: 1.1*10 7 , visit II = 2.4*10 5 (p = 0.002)). No statistically significant reduction of cell-free bacterial DNA was detected (PB: visit I: 6.1*10 5 , visit II: 1.6*10 5 (p = 0.08); SE: visit I: 5.3*10 5 , visit II: 2.9*10 5 (p = 0.10)). The decrease of intact cell-derived (p = 0.371) and cell-free DNA (p = 0.455) did not differ significantly between PB and SE. Lactobacillus was most abundant within the microbial community at both visits. Alpha-diversity was not affected by treatment and samples showed high intra- and interindividual diversity., Conclusion and Clinical Significance: Both self-etch adhesives have an antibacterial effect due to a decrease of bacterial DNA after selective caries removal. However, the results do not reveal any additional antibacterial effect by MDPB. The study is registered with the German Clinical Trials Register (DRKS00011532)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The authors conducted a case series to determine arrest of root surface caries lesions in older adults when teeth were treated topically with 38 % silver diamine fluoride (SDF)., Methods: The study was a prospective, single center case series. The patients were 62 older adults (age ≥55 years) who sought treatment at a dental school clinic. To be included, a patient needed to have at least one active root caries lesion. Lesions were rinsed and then dried with air, isolated, and then 38 % SDF was applied for two minutes with a microbrush. Treated lesions were re-evaluated at 2-3 weeks. Treatment was repeated every six months. Survival analysis methods for clustered data were used to estimate the caries lesion arrest probability over time separately for root surfaces and at crown margins., Results: Fifty-five participants returned for follow-up (44 % female, mean age (SD) 79.8 (7.4)). The probability of a lesion arresting with treatment ranged from 82.9 to 91.6%. Arrest rates at 18 months were slightly higher in root surfaces than around crown margins, 91.6 % (95 % CI 69.1-97.1) versus 89.8 % (95 % CI 71.6-96.3). All furcal lesions (n = 7) were arrested by 6 months, 100 % (95 % CI 59-100)., Conclusion and Clinical Significance: Repeated application of 38 % SDF at 6-month intervals was effective in arresting decay of root surface lesions and lesions around crowns in older adults. Study outcomes support SDF treatment for older adult patients who are frail and residing in nursing homes or dependent living facilities., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To examine the enamel fluoride uptake and remineralization potential of arginine-fluoride (Arg-NaF) varnishes in a simulated clinical condition using a multi-species bacterial pH-cycling model., Methods: L-Arginine (at 1 %, 2 %, and 4 % by wt.) was incorporated in a 5 % NaF varnish. Experimental and control groups were: 1 % Arg-NaF; 2 % Arg-NaF; 4 % Arg-NaF; NaF and no treatment. Artificial incipient caries-like lesions were formed on 30 enamel specimen blocks (n = 6). The specimens underwent multi-species bacterial pH-cycling in an artificial mouth system using oral biofilm reactor for 72 h after treatment. The specimens were evaluated for mineral density using micro-CT, Ca/P ratio with SEM-EDX, enamel fluoride uptake (EFU) and plaque fluoride uptake (PFU)., Results: Increasing concentrations of Arg in NaF varnish significantly increased the EFU of incipient caries-like lesions (p < 0.001). The PFU for 1 % Arg-NaF was significantly higher than 4 % Arg-NaF and the control NaF (p < 0.05). Post pH-cycling, Ca/P ratio with 1 %/2 % Arg-NaF was closest to hydroxyapatite (1.67). Mineral gain and % remineralization of 1 %/2 % Arg-NaF was significantly higher than the control NaF varnish (p < 0.05)., Conclusion: The prebiotic L-arginine (at 1 %/2 % by wt.) in a 5 % NaF varnish enhanced the enamel fluoride uptake and remineralization potential of the conventional 5 % NaF varnish., Clinical Significance: The Arg-NaF varnish addresses the limitations of fluorides on cariogenic biofilms. The Arg-NaF varnish appears a promising caries-preventive regimen that counters the pathogenic biofilms by Arg and promotes remineralization with fluorides. In high caries-risk patients, professional application of Arg-NaF varnish might aid to alleviate the global burden of dental caries., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the remineralising and staining effects of sodium fluoride (NaF) with silver nanoparticles (AgNPs) on artificial dentine caries., Methods: Human dentine blocks with artificial caries were divided into four groups. Group 1 received 5 % NaF (22,600 ppm fluoride) with 4000 ppm AgNPs; group 2 received 4000 ppm AgNPs; group 3 received 5 % NaF, group 4 received deionised water (negative control). All groups underwent three biochemical cycles. Each cycle included Streptococcus mutans biofilm challenge and remineralisation process. The lesion depth, mineral-organic content, surface morphology and crystal characteristics of dentine blocks were evaluated using micro-computed tomography, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM) and X-ray diffraction. Colour change of dentine blocks was assessed using spectrophotometry., Results: The mean lesion depths of groups 1-4 were 151.13 ± 29.13 μm, 172.38 ± 23.44 μm, 190.41 ± 32.81 μm and 221.24 ± 27.91 μm, respectively. The hydrogen phosphate-to-amide I ratios of groups 1-4 were 5.98 ± 0.36, 3.86 ± 0.56, 4.00 ± 0.67 and 2.53 ± 0.40, respectively. There was no significant interaction effect between AgNPs and NaF. SEM showed less exposure of dentine collagen fibres in group 1 when compared to other groups. X-ray diffraction revealed presence of silver chloride and metallic silver in group 1 and 2. There was no significant difference in colour change among the four groups (p = 0.74)., Conclusions: NaF solution with AgNPs can remineralise dentine caries without staining., Clinical Significance: Sodium fluoride solutions that include silver nanoparticles have potential uses in the management of caries., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To investigate the microbiome profile and relative abundance changes of the plaque on silver diamine fluoride (SDF)-treated caries in children with early childhood caries., Methods: A single trained examiner assessed the caries as being arrested or active and then collected plaque samples from the caries lesions from fourteen 5-year-old children immediately before, 2 weeks after, and 12 weeks after a one-off application of 38 % SDF. We assigned 16S rRNA gene sequences to operational taxonomic units (OTUs) using a 98.5 % identity cut-off. We also used a variety of taxonomy- and phylogeny-based statistical approaches to compare the biodiversity and relative abundance among different groups., Results: The caries arrest rate were 90 % and 83 % after 2 and 12 weeks, respectively. We studied 46 plaque samples and identified 388 OTUs (254 identified at the species level, 129 identified at the genus level, and 76 identified at the family level). There was no significant change in the diversity in the arrested caries before and 12 weeks after SDF treatment (p = 0.71). The diversity in active caries reduced significantly 12 weeks after SDF treatment (p = 0.006). The relative abundance of certain caries-related species (e.g., Streptococcus mutans and Lactobacillus sp.) was reduced in arrested caries but was increased in active caries after SDF treatment., Conclusion: There was no overall microbiome changes in the caries arrested by SDF. The relative abundance of some caries-related species is reduced in arrested caries, while increased in active caries., Clinical Significance: This study provides information on microbiome changes on SDF-treated caries of children., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To compare the success rates of restoring untreated and SDF-treated dentine caries lesions in primary teeth with atraumatic restorative treatment (ART) approach., Method: Cavitated dentine caries lesions in preschool children were randomly allocated to two groups to be applied with either 38% silver diamine fluoride (SDF) solution or tonic water (control) ten weeks before being restored with the ART approach. Status of the restorations were assessed every six months by a blinded independent examiner. Multilevel logistic regression and multilevel survival analyses were conducted to assess the restoration success rates., Results: A total of 194 children (SDF group, 101; control group, 93) were included, with 260 and 249 ART restorations placed in the SDF and the control groups, respectively. At 24-month follow-up, 88 (87 %) and 84 (90 %) children remained in the SDF and the control groups, respectively. There was no significant difference between the ART restoration success rates of the two study groups (p > 0.05). The success rate of ART restorations was associated with the class of restorations. Class I restorations had the highest success rate (∼50 %), followed by Class V (∼35 %), Class II (∼15 %) and Class III (<10 %). Besides, the mean time used to place an ART restoration in a SDF-treated caries lesion was shorter than that in untreated lesion (4.8 vs. 5.1 min, p = 0.006)., Conclusion: Prior SDF application does not significantly affect the success rate of ART restorations placed in primary teeth. Besides, it is faster to place ART restorations in caries lesions that have been previously treated with SDF., Clinical Significance: Prior application of silver diamine fluoride solution on cavitated dentine caries lesions in primary teeth can shorten the average time required to place an ART restoration while not jeopardizing the success rate of the restorations., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To examine the effect of incorporating arginine in a 5% sodium fluoride (NaF) varnish on its remineralization potential and HGF-1 cytotoxicity., Methods: Experimental varnishes were prepared using two arginine variants: l-arginine (Arg) and l-arginine monohydrochloride (Arg.HCl) at 2%, 4%, & 8% w/v. with control 5% NaF varnish. Sound enamel specimens with varnish treatments were subjected to a 4-day demineralization assay and surface roughness analysis using AFM (n = 3). Enamel specimens with artificial incipient caries-like lesions were subjected to a remineralization assay (n = 6) and an 8-day pH-cycling (n = 3). For remineralization assay, enamel F/Arg-uptake and Ca/PO 4 3- i-content were estimated. During pH-cycling, EDX mapping for Ca/F-content and mineral density using micro-CT were assessed. The HGF-1 cytotoxicity of the varnishes was examined using MTT/CCK-8 assay., Results: The Ca-content/F-uptake of the 2% Arg-NaF varnish treated specimens were significantly higher than other varnishes (p < 0.05). The 2% Arg-NaF had significantly higher remineralization potential than NaF (p < 0.001), suggesting Arg-Ca-F complex formation post-varnish application. The 8% Arg-NaF exhibited significantly more pronounced cytotoxicity to HGF-1 cells than 2% Arg-NaF (p < 0.001) and NaF varnish., Conclusions: Incorporation of 2% Arg in NaF varnish enhanced the enamel remineralization potential of NaF varnish; while 8% Arg in NaF varnish was cytotoxic to HGF-1., Clinical Significance: A professionally deliverable l-arginine-enriched NaF varnish for caries prevention addresses a global public health priority. The synergism between l-arginine and NaF varnish counters the limited antimicrobial effects of fluorides and supports acquisition of a balanced oral microbiome. The combined arginine-fluoride varnish will provide the much-needed ecological-based approach for caries prevention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The study aimed to compare the effectiveness of 38% silver diamine fluoride (SDF) solution, and 5% sodium fluoride (NaF) varnish applied semiannually in arresting dentin caries in young children with high caries risk., Methods: Children aged 1-3 years who had at least one active dentin carious lesion were randomly allocated into 2 groups as follows: Group 1 = 38% SDF (Topamine), and Group 2 = 5% NaF varnish (Duraphat). Both agents were applied every 6 months onto the carious surface. Lesion activity was assessed by the visual-tactile examination. Baseline and follow-up examinations were conducted by the same examiner. The children's demographic background, oral health-related habits, and oral hygiene practices, as well as parental satisfaction with children's dental appearance were collected at baseline and the 12-month follow-up., Results: At baseline, 153 and 149 children were recruited in Group 1 and Group 2, respectively. The mean dmfs scores in Groups 1 and 2 were 8.89 and 9.79, respectively. After 12 months, 87.1% remained in the study. The caries arrest rate of Group 1 (35.7%) was significantly higher than that of Group 2 (20.9%) (p < 0.001). The results of the multilevel logistic regression analysis confirmed that the treatment in Group 1 was more effective in arresting dentin carious lesions than that of Group 2 (OR = 2.04; 95% CI, 1.41-2.96). The presence of plaque on caries lesions, tooth type, tooth surface type, frequency of milk feeding, snack taking, and family income influenced on caries activity. Regardless of the intervention groups, there were no differences in parental satisfaction with on the child's dental appearance before and after receiving the intervention., Conclusion: Based on the 12-month results, 38% SDF is more effective than 5% NaF varnish in arresting dentin carious lesions in young children. SDF has no negative impact on parental satisfaction with the child's dental appearance., Clinical Significance: To control dentin carious lesions in young children with high caries risk, 38% SDF is more effective than 5% NaF varnish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To compare human versus bovine enamel when used in microbial caries models; and to evaluate the use of nylon mesh to support biofilm growth over enamel., Methods: Twenty-four sub-subgroups were included (time factor: 4, 8, and 12 days; substrate factor: human/bovine; mesh factor: yes/no; treatment factor: 18.4 mM NaF (350 ppm F), de-ionized water [DIW]; n = 9/sub-subgroup). Microcosm biofilm from human saliva (IRB approval #1,406,440,799) was grown on enamel specimens for 24-h (Brain Heart Infusion media; 0.2 % sucrose), using active attachment model. Then, pH-cycling took place. At the end of each pH-cycling period, enamel specimens were analyzed: surface microhardness (VHN change ); transverse microradiography (integrated mineral loss [ΔZ], lesion depth [L]). Biofilm was analyzed: lactic acid production (LDH activity); exopolysaccharide (EPS) amount; and viability (12-day sub-groups). Data were analyzed using ANOVA at a 5 % level of significance., Results: The three-way interaction between pH-cycling duration, substrate type, and treatment type was significant for (VHN change [p < 0.0005], ΔZ [p = 0.0027], and L [p < 0.0001]). VHN change exhibited increased lesion severity as pH-cycling time increases, in both treatments. VHN change data indicated a treatment effect in all timepoints. ΔZ and L exhibited higher values with more mature biofilms. ANOVA analyses for LDH and EPS indicated a significance between variables (LDH p = 0.0100; EPS p < 0.0001). Mesh-covered specimens resulted in lower LDH and EPS values in all maturations. ANOVA analyses of viability (12 days) between variables was significant., Conclusion: within the study's limitations, human or bovine enamel can be used in microbial in vitro caries models to study biofilm's maturation and anticaries agents., Clinical Significance: This study demonstrated how a known cariostatic effect of a fluoride concentration in toothpastes can be modulated by the maturation stage of oral biofilm. This can represent hard to reach areas in the oral cavity (e.g. in orthodontic patients or patients with intermaxillary fixation following oral and maxillofacial surgeries)., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: This in vitro study investigated the effect of theobromine on the de- and remineralization of enamel carious lesions under plaque fluid-like conditions., Methods: Early carious lesions were created in 272 bovine enamel specimens and assigned to sixteen groups (n=17) based on Knoop surface microhardness (SMH). Lesions were demineralized again under plaque fluid-like conditions in the presence of fluoride (0.2 or 1ppm) and theobromine (0; 10; 100 or 200ppm) at different pH values (5.5 or 7.0) in a factorial design. SMH was determined again and percent SMH recovery (%SMHr) calculated. Three-way ANOVA was used for the fixed effects of fluoride, theobromine and pH levels to compare the differences between each level., Results: The three-way interaction was not significant (p=0.712). The two-way interaction between fluoride and pH was significant (p=0.030), whereas those between fluoride and theobromine as well as that for pH and theobromine were not (p=0.478 and p=0.998, respectively). Theobromine did not affect %SMHr at any of the tested concentrations. There were trends for the higher fluoride concentration and the higher pH resulting in more rehardening with the lesions exposed to 0.2ppm fluoride at pH 5.5 displaying significantly less rehardening than those exposed to 0.2ppm fluoride at pH of 7.0 and lesions exposed to 1ppm fluoride at pH of 5.5., Conclusion: Theobromine, when continuously present in a plaque fluid-like medium at various concentrations and at different pH values, does not affect de- or remineralization of enamel carious lesions under the presently studied conditions., Clinical Significance: Based on the presently available evidence, theobromine cannot be recommended as an anticaries agent., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: This laboratory study investigated the ability of dual whitening anti-caries mouthrinses to remove extrinsic staining from artificially stained caries lesions and to enhance their remineralization and fluoridation., Materials and Methods: Early caries lesions were created in bovine enamel specimens. The lesions were artificially stained and pH cycled for 10 days with the daily cycling regimen consisting of twice daily 60s-treatments with one of 11 mouthrinses, a 4-h demineralization period and artificial saliva treatments in between. Mouthrinses were eight commercially available products, all containing 100ppm fluoride but utilizing hydrogen peroxide, pyro-, tri- or hexametaphosphate salts and/or sodium bicarbonate. The three control mouthrinses were 100ppm fluoride, 30 % hydrogen peroxide and deionized water. Enamel color changes (ΔE) were determined spectrophotometrically. Vickers surface microhardness (VHN) was used to determine lesion remineralization. Enamel fluoride content (EFC) was determined using the microbiopsy technique. Data were analyzed using ANOVA., Results: ΔE was significantly different among groups (p=0.0045). Thirty percent hydrogen peroxide was superior to all other mouthrinses, while there were no differences between commercial mouthrinses and deionized water. There were small, directional but non-significant differences between commercial mouthrinses with those containing hydrogen peroxide providing better whitening. There were no significant differences between mouthrinses in their ability to remineralize caries lesions (p=0.2898). EFC differed among groups (p<0.0001), with the two mouthrinses containing pyrophosphate salts having lower EFC than all but the deionized water group., Conclusions: Artificially stained caries lesions show reduced susceptibility to fluoride remineralization and whitening effects of commercial whitening and anti-caries mouthrinses., Clinical Relevance: Artificially stained caries lesions appear to require stronger than over-the-counter interventions to successfully whiten and remineralizing them., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this split-mouth, randomized, controlled clinical trial was to evaluate the efficacy of resin infiltration in controlling the progression of non-cavitated proximal lesions in primary molars after two-years follow-up., Methods: Fifty healthy children presenting at least two primary molars with proximal lesion detected radiographically (in the inner half of enamel or the outer third of dentin) were included in the study. The proximal lesions were randomly allocated into resin infltration + flossing (test group) or flossing (control group). All patients received oral hygiene instructions for daily brushing with fluoride toothpaste (1100 ppmF) and flossing. The proportion of caries progression was compared using the McNemar test. The main outcome after 2-years, caries progression in the radiography was assessed by pair-wise reading by an independent examiner who was blind regarding the treatment., Results: The sample comprised 28 (56%) girls and 22 (44%) boys with a defs of 7,3 (SD = 6,5), mainly of moderate (46%) to high (48%) caries risk. Results after one year were published previously. After 2-years, 29 (58%) patients were assessed. Caries progression was observed in 24.1% (7/29) of the test lesions, compared with 55.2% (16/29) of the control lesions (p = 0.012). The therapeutic effect was 31.1% and the relative risk reduction (RRR) was 56.3%. Eigth lesions from the control group and two lesions from the test group progressed to the inner third of dentin and were restored., Conclusions: In conclusion, resin infiltration was more efficacious in controlling proximal caries lesions in primary molars than non-invasive approach alone., Clinical Significance: The results indicate that resin infiltration was an efficacious method in controlling proximal caries lesions in primary molars after 2 years, even in patients with high caries risk, reaffirming the results of 1-year follow-up., (Copyright © 2019. Published by Elsevier Ltd.)

Objectives: The objectives of this study were to develop a resin-modified glass ionomer containing nanoparticles of calcium fluoride (nCaF 2 ) and dimethylaminohexadecyl methacrylate (DMAHDM) for the first time and investigate the antibacterial and remineralization properties., Methods: nCaF 2 was synthesized using a spray-drying method and characterized using a transmission electron microscope. Twenty weight percentage (wt%) nCaF 2 and 3 wt% DMAHDM were incorporated into a RMGI (GC Ortho LC). Enamel shear bond strength (SBS) and cytotoxicity were determined. Fluoride (F) and calcium (Ca) ion releases were assessed. Biofilm live/dead staining, metabolic activity, polysaccharide and lactic production, and colony-forming units (CFU) were evaluated. The remineralization ability was determined by measuring the effects of cements on enamel surface hardness and lesion depth., Results: Incorporating 20 wt% nCaF 2 and 3 wt% DMAHDM did not compromise the SBS (p > 0.1). The decrease of pH from 7.0 to 4.0 significantly increased the F and Ca ion releases. The new cement greatly reduced the metabolic activity, polysaccharide and lactic acid productions, and lowered the biofilm CFU by 3 log, compared to commercial control (p < 0.05). The new cement increased the enamel hardness by 56% and decreased the lesion depth by 43%, compared to control (p < 0.05). The cell viability at 7 days against the new cement extracts was 82.2% of that of the negative control in culture medium without any extracts., Conclusions: The novel orthodontic cement containing nCaF 2 and DMAHDM achieved much stronger antibacterial and remineralization capabilities and greater enamel hardness than the commercial control did, without compromising the orthodontic bracket-enamel SBS and biocompatibility., Clinical Significance: The novel bioactive and nanostructured orthodontic cement is promising to inhibit enamel demineralization, white spot lesions and caries in orthodontic treatments., (Published by Elsevier Ltd.)

Objectives: To find out the effects of placement of atraumatic restorative treatment (ART) restorations on parental satisfaction and oral health related quality of life (OHRQoL) of preschool children with SDF-treated or untreated dentine caries lesions., Methods: In a randomized controlled trial conducted in Hong Kong, preschool children who had cavitated dentine caries lesions were randomly assigned to receive application of silver diamine fluoride (SDF) solution or placebo (tonic water) on their caries lesions 10 weeks before receiving ART restorations. Parents were asked to rate their satisfaction with their child's teeth using a 5-point scale (5 = very satisfied, 1 = very dissatisfied) before and six months after the restorative treatment. Besides, the Chinese version of Early Childhood Oral Health Impact Scale (C-ECOHIS) was used to assess the children's OHRQoL., Results: A total of 194 children participated in this study, with 101 and 93 children receiving SDF and placebo application before ART restorations, respectively. There was no significant difference in parental satisfaction and C-ECOHIS score between the SDF and placebo groups at baseline. At the 6-month follow-up, the mean parental satisfaction score regarding their child's dental health status increased significantly (p < 0.001) from 2.2 ± 0.7 to 2.8 ± 1.0 in the SDF group and from 2.3 ± 0.8 to 2.7 ± 0.9 in the placebo group. However, no significant changes (p > 0.05) in C-ECOHIS scores were found in either of the two groups after ART restoration placement., Conclusions: Placement of ART restorations can improve parental satisfaction with the health and appearance of their child's teeth but has no significant effect on the OHRQoL., Clinical Significance: This study provides valuable information about the effects of ART restoration placement on SDF-treated or untreated dentine caries lesions regarding parental satisfaction and OHRQoL of preschool children., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: This clinical trial investigated the efficacy of silver diamine fluoride (SDF) in arresting dentine caries in primary molars of preschoolers. Time required for treatment, adverse effects, parental aesthetic perception, anxiety and oral health related to quality of life (OHRQoL) was evaluated., Materials and Methods: Children, 2-5 years old, with active dentine caries lesions on the occlusal surface of primary molars were randomly allocated to test group (SDF) or control group (atraumatic restorative treatment/ART). The dmf-t/DMF-T and ICDAS indexes determined the presence of caries and activity. The main outcome after 3, 6 and 12-month follow-up was assessed by a blind examiner. The time required to perform the treatments was recorded and a facial image scale was applied to assess anxiety before and after treatment. Adverse events and aesthetic perception were assessed through questions addressed to caregivers; and the OHRQoL through the B-ECOHIS questionnaire., Results: In 68 patients that were randomized, the mean number of treated teeth per child was 2.42(1.04) and 2.09(1.18) in the SDF and ART groups (p = 0.074), respectively. The mean difference of arrested lesions between the groups after 12 months was -0,07(0.05; - 0.17-0.30). The time required to treat with SDF was lower than the ART (p < 0.001). There was no difference in the percentage of adverse events + aesthetic perception (p = 0.709), and the change in anxiety (p = 0.155). There was a less impact in OHRQoL after ART treatment, but only when the parents' distress subscale was considered (p = 0.012)., Conclusion: SDF requires much less chair-time and have similar results as ART in arresting caries lesion, anxiety, adverse effects, aesthetic perception and quality of life., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the remineralising effect and bacterial growth inhibition of 38% silver diamine fluoride (SDF) solution and 5% sodium fluoride (NaF) varnish on artificial dentine caries lesions., Methods: Demineralised dentine blocks were treated with SDF + NaF (Group 1), SDF (Group 2), NaF (Group 3) and water (Group 4) and subjected to a Streptococcus mutans biofilm challenge. Lesion depth, precipitates' characteristics and matrix (collagen)-to-mineral ratio were evaluated by micro-computer tomography (micro-CT), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), respectively. The biofilm kinetics, viability and topography were assessed by counts of colony forming units (CFUs), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), respectively. Data were analysed by two-way ANOVA test., Results: The lesion depths of Groups 1-4 were 170 ± 28 μm, 160 ± 32 μm, 353 ± 38 μm and 449 ± 24 μm, respectively. The addition of NaF to SDF did not show better remineralisation than SDF (p = 0.491). Metallic silver and silver chloride were found in Groups 1 and 2. The amide I-to-hydrogen phosphate ratios of the four groups were 0.14 ± 0.02, 0.14 ± 0.01, 0.29 ± 0.05 and 0.49 ± 0.16, respectively, and the addition of NaF to SDF did not offer better protection against collagen exposure than SDF (p = 0.986). The Log 10 CFUs of Groups 1-4 were 5.75 ± 0.56, 4.49 ± 0.57, 6.55 ± 0.39 and 6.40 ± 0.38, respectively. The presence of NaF reduced the antibacterial effect of SDF (p < 0.001). The SEM and CLSM images supported the findings., Conclusion: Application of SDF with or without NaF reduced the demineralisation of dentine caries, but SDF exerted stronger inhibition of biofilm growth than SDF with NaF., Clinical Significance: NaF varnish affects the antibacterialeffects of SDF, the adjunctive application of SDF solution and NaF varnish is not recommended to arrest dentine caries in clinic., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the influence of zinc oxide quantum dots (ZnO QDs ) into an experimental adhesive resin regarding the antibacterial activity against Streptococcus mutans and the cytotoxicity against pulp fibroblasts., Materials and Methods: ZnO QDs were synthesized by sol-gel process and were incorporated into 2-hydroxyethyl methacrylate (HEMA). An experimental adhesive resin was formulated by mixing 66.6 wt.% bisphenol A glycol dimethacrylate (BisGMA) and 33.3 wt.% HEMA with a photoinitiator system as control group. HEMA containing ZnO QDs was used for test group formulation. For the antibacterial activity assay, a direct contact inhibition evaluation was performed with biofilm of Streptococcus mutans (NCTC 10449). The cytotoxicity assay was performed by Sulforhodamine B (SRB) colorimetric assay for cell density determination using pulp fibroblasts. Data were analyzed by Student's t-test (α = 0.05)., Results: The antibacterial activity assay indicated statistically significant difference between the groups (p = 0.003), with higher values of biofilm formation on the polymerized samples of control group and a reduction of more than 50% of biofilm formation on ZnO QDs group. No difference of pulp fibroblasts viability was found between the adhesives (p = 0.482)., Conclusion: ZnO QDs provided antibacterial activity when doped into an experimental adhesive resin without cytotoxic effect for pulp fibroblasts. Thus, the use of ZnO QDs is a strategy to develop antibiofilm restorative polymers with non-agglomerated nanofillers., Clinical Significance: ZnO QDs are non-agglomerated nanoscale fillers for dental resins and may be a strategy to reduce biofilm formation at dentin/restoration interface with no cytotoxicity for pulp fibroblasts., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Rechargeable calcium phosphate (CaP) composites were developed recently. However, none of the rechargeable CaP composites was antibacterial. The objectives of this study were to develop the first rechargeable CaP composite that was antibacterial, and to investigate the effects of adding dimethylaminohexadecyl methacrylate (DMAHDM) into rechargeable CaP composite on ion rechargeability and re-release as well as biofilm properties., Methods: DMAHDM was synthesized via a Menschutkin reaction. Nanoparticles of amorphous calcium phosphate (NACP) were synthesized using a spray-drying technique. The resin contained ethoxylated bisphenol A dimethacrylate (EBPADMA) and pyromellitic glycerol dimethacrylate (PMGDM). Two composites were fabricated: rechargeable NACP composite, and rechargeable NACP-DMAHDM composite. Mechanical properties and ion release and recharge were measured. A dental plaque microcosm biofilm model using saliva was tested., Results: Flexural strength and elastic modulus of rechargeable NACP and NACP-DMAHDM composites matched commercial control composite (p > 0.1). NACP-DMAHDM inhibited biofilm metabolic activity and lactic acid, and reduced biofilm colony-forming units (CFU) by 3-4 log. NACP and NACP-DMAHDM showed similar Ca and P ion recharge and re-release (p > 0.1). Therefore, adding DMAHDM did not compromise the ion rechargeability. One recharge yielded continuous release for 42 d. The release was maintained at the same level with increasing number of recharge cycles, indicating long-term ion release and remineralization capability., Conclusions: The first CaP rechargeable and antibacterial composite was developed. Adding DMAHDM into the rechargeable NACP composite did not adversely affect the Ca and P ion release and recharge, and the composite had much less biofilm growth and lactic acid production, with CFU reduction by 3-4 log., Clinical Significance: This novel CaP rechargeable composite with long-term remineralization and antibacterial properties is promising for tooth restorations to inhibit caries., (Copyright © 2018 Elsevier Ltd. All rights reserved.)