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ial composition revealed in endodontic patients who had recently received systematic antibiotic therapy.The pH value of a biofilm influences the pathogenesis and therapy of oral diseases such as caries and periodontitis. This study aimed to investigate the influence of different initial pH values on the microbial composition, bacterial counts, metabolic activity, and quantity of three defined biofilms representing oral health, caries, and periodontal disease. Respective bacterial suspensions in the nutrient broth were initially adjusted to pH values between 5 and 8. Then biofilms were cultured on polystyrene surfaces coated with a proteinaceous solution for 2 h ("healthy" biofilm), 6 h ("healthy," and "cariogenic" biofilms), 24 h ("cariogenic," and "periodontitis" biofilms), and 48 h ("periodontitis" biofilm). In all biofilms, total bacterial counts were lower at an initial pH of 5 or 5.5 than at higher pH values. In the biofilm representing caries, the percentage of cariogenic bacteria (Streptococcus mutans, S. sobrinus, Lactobacillus acidophilus) was higher at a low pH, the metabolic activity was highest at pH 6-6.5, and biofilm mass was greatest at pH 7-7.5. In the biofilm representing periodontitis, the percentage of Porphyromonas gingivalis increased with the pH. selleck inhibitor Also, the metabolic activity was highest at pH 8, whereas mass had the highest value at pH 7. In conclusion, the initial pH value influences biofilm formation. In particular, metabolic activity and the amount of bacteria associated with disease correlated with the respective pH known to be of importance in the development of caries (relatively low pH) and periodontitis (higher pH). Modifying the pH level in oral biofilms might be an alternative concept in (primary) prevention and treatment, not only of caries but also of periodontitis.Biofilm formation depends on many factors, one of them being the surface (substrate) on which the biofilm is formed, and dental restorative materials are such substrates. Biofilms play a crucial role for caries formation and inflammation of gingival, periodontal, or mucosal tissues next to restorations. Even general health problems such as systemic infections in immunocompromised patients may result from biofilms on dental materials (e.g., on dentures). Furthermore, biofilms may change material or surface properties. Biofilms on restorative materials have been investigated by several in vitro, in situ, and in vivo methods measuring a large number of different endpoints. Basically, datasets obtained from different methodological approaches are most suitable for final assessments. While surface properties like wettability or surface free energy (SFE) influence biofilm formation to a certain extent, the most relevant surface properties are material roughness followed by surface chemistry. The pellicle, which is formed rapidly on restorations after in vivo exposure, masks or levels off the influence of surface properties like wettability or SFE on biofilm formation. The prevention of biofilm formation is mainly based on general oral hygiene regimens. Furthermore, optimal polishing of restorative materials is instrumental. Several antimicrobial substances have been incorporated into restorative materials, which act by being released or as surface repellents. However, the optimal biofilm-preventive restorative material has not been found so far. New approaches in this context should aim at (1) better understanding the role of the biofilm matrix (extracellular polymeric substance), and (2) implementing ecology-based approaches for the modification of dysbiotic disease-associated biofilms.The formation of a physiological biofilm cannot be avoided under normal circumstances. However, the consequences of a supragingivally located biofilm, such as caries, gingivitis and, as a further effect, periodontitis, are relatively easy to avoid. The simplest and most common method used worldwide for the elimination of biofilm is periodic mechanical removal using a toothbrush or similar tools, such as chewing sticks or woods. This method was already used in ancient Egypt, and is still being used today, albeit advanced and improved with the help of toothpastes. Here we give a summary of the most common toothbrushes, highlighting their advantages and disadvantages. Furthermore, we provide an overview of the most common toothpastes, their ingredients, and functions. In addition, the ingredients will be critically evaluated and recommendations given for the use or non-use of certain ingredients for different target groups, such as children, healthy adults, or patients with special needs.BACKGROUNDAlthough CDK4/6 inhibitors are an established treatment for hormone receptor-positive, HER2-negative metastatic breast cancers, their benefit in other malignancies remains limited.METHODSWe investigated factors associated with clinical outcomes from CDK4/6 inhibitor-based therapy among patients with G1/S phase cell-cycle alterations (CDK4/6 amplifications, CCND1/2/3 amplifications, or CDKN2A/B alterations).RESULTSOverall, 2457 patients with diverse solid tumors that underwent clinical-grade, next-generation sequencing (182-465 genes) and therapy outcome of (non-breast cancer) patients treated with matched CDK4/6 inhibitors were analyzed. G1/S phase cell-cycle alterations occurred in 20.6% (507 of 2457) of patients; 99% of those patients (n = 501) harbored ≥1 characterized co-alteration (median, 4; range, 0-24). In 40 patients with G1/S phase cell-cycle alterations given CDK4/6 inhibitors as part of their regimen, significantly longer median progression-free survival (PFS) was observed when CDK4/6 inhibitor-based therapies matched a larger proportion of tumor alterations, often because CDK4/6 inhibitors were administered together with other drugs that were matched to genomic co-alterations, hence achieving a high matching score (high vs. low [≥50% vs. less then 50%] matching score, PFS, 6.2 vs. 2.0 months, P less then 0.001 [n = 40] [multivariate]) and higher rate of stable disease ≥6 months or an objective response (57% vs. 21%, P = 0.048).CONCLUSIONIn summary, in cell-cycle-altered cancers, matched CDK4/6 inhibitors, as part of an individualized regimen targeting a majority of genomic alterations, was independently associated with longer PFS.TRIAL REGISTRATIONClinicalTrials.gov NCT02478931.FUNDINGJoan and Irwin Jacobs Fund, National Cancer Institute (P30 CA023100, R01 CA226803), and the FDA (R01 FD006334).
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