Human papillomavirus-driven head and neck cancers in Japan during 2008-2009 and 2018-2019: The BROADEN study.

There is limited understanding of epidemiology and time trends of human papilloma virus (HPV)-driven head and neck cancers (HNC) in Japan, especially outside of the oropharynx. To assess HPV-driven HNC, a non-interventional study (BROADEN) of HNC patients diagnosed in 2008-2009 and 2018-2019 was conducted in Japan. Adult patients with oropharyngeal, nasopharyngeal, laryngeal, hypopharyngeal or oral cavity cancers were included in this study. HPV was centrally tested using p16INK4a immunohistochemistry, HPV-DNA PCR and HPV E6*I mRNA. HPV attributability required positivity in at least two tests (p16INK4a immunohistochemistry, HPV-DNA PCR, HPV E6*I mRNA) in the oropharynx, and HPV-DNA and HPV E6*I mRNA positivity for non-oropharynx sites. Nineteen hospitals included a total of 1108 patients, of whom 981 had valid samples. Men accounted for 82% of HNC diagnoses. Patients in the earlier cohort were younger and included a higher percentage of smokers. There was an increasing trend of HPV-driven oropharyngeal cancer over the last decade, from 44.2% to 51.7%. HPV attribution in nasopharyngeal cancers was 3.2% in 2008-2009 and 7.5% in 2018-2019; and 4.4% and 0% for larynx respectively. In total, 95.2% of HPV-driven HNC were attributed to HPV genotypes included in the 9-valent HPV vaccine being HPV16 the most prominent genotype. These results suggest that an epidemiologic shift is happening in Japan, with a decrease in smoking and alcohol use and an increase in HPV-driven HNC. The increasing trend of HPV-driven HNC in Japan highlights the need for preventive strategies to mitigate the rise of HPV-driven HNC.

ß-Glycyrrhetinic acid inhibits the bacterial growth and biofilm formation by supragingival plaque commensals.

ß-Glycyrrhetinic acid (BGA) is a natural antibacterial agent. Previous studies reported that BGA has antibacterial effects against several bacteria. This study evaluated the effects of BGA on the regulation of supragingival plaque bacteria. First, the minimum inhibitory concentrations (MICs) of BGA against oral bacteria were measured. Next, the minimum concentrations for inhibition of biofilm formation were evaluated against Streptococcus mutans and Streptococcus sobrinus, possessing insoluble glucan synthesis abilities. The MICs of biofilm formation by these bacteria ranged from 1/8 to 2× MIC. Furthermore, the inhibition effects of BGA against the coaggregation of Porphyromonas gingivalis and Streptococcus gordonii were evaluated. BGA at 32 or 64 µg/mL inhibited the coaggregation of these bacteria after a 30 min incubation. Lastly, the inhibition effects of BGA against human supragingival plaque bacteria were evaluated. Human supragingival plaque samples were obtained from 12 healthy donors. The inhibition effects of BGA against biofilm formation by these plaque bacteria were evaluated. Of 12 samples, the biofilm formation by 11 was significantly attenuated by 128-256 µg/mL of BGA. The number of colony forming units in these biofilms was also significantly attenuated. In conclusion, it was revealed that BGA inhibits the growth and biofilm formation of bacteria, furthermore, the same effect was confirmed with supragingival plaque bacteria. BGA is a good candidate for a natural agent that prevents the outbreak and progression of periodontal disease because it suppresses not only the growth and biofilm formation of bacteria, but also the coaggregation of P. gingivalis with plaque bacteria.

Age-related changes in gingival blood flow parameters measured using laser speckle flowmetry.

Previous studies have suggested a possible relationship between age-related changes to human gingival hemodynamics and periodontal disease. However, firmly establishing this has been difficult because of a lack of suitable tools. Our study investigated whether a non-invasive laser speckle flowgraphy (LSFG)-based 2-dimensional technique could be used to assess maxillary anterior gingival blood flow under resting conditions. In total, 124 healthy male volunteers aged between 22 and 69 years were included in the study and delineated into young (Y; 22-37 years, n = 45), middle-aged (M; 38-53 years, n = 43), and elderly groups (E; 54-69 years, n = 36). The differences in gingival hemodynamics were compared among age groups and pulse waveform analysis performed to calculate blood flow indices, mean blur rate (MBR), gingival vascular conductance (MBR/mean blood pressure [MBP]), and three pulse waveform parameters (acceleration time index [ATI], falling rate, and blowout time [BOT]). Although no statistically significant differences were observed in the MBR of the three age groups, vascular conductance (MBR/MBP) was lower in groups M and E compared to group Y and correlated negatively with age. ATI and falling rates were also significantly higher in group E relative to group Y, whereas average BOT was significantly lower. All of the assessed parameters correlated with age. These data suggest that there are age-related decreases in the ability to maintain blood flow in the human maxillary anterior gingiva under resting conditions which may impact the likelihood of periodontal disease.

A single nucleotide polymorphism in 3'-untranslated region contributes to the regulation of Toll-like receptor 4 translation.

We have previously shown that a single nucleotide polymorphism rs11536889 in the 3'-untranslated region (UTR) of TLR4 was associated with periodontitis. In this study the effects of this single nucleotide polymorphism on Toll-like receptor (TLR) 4 expression were investigated. Monocytes from subjects with the C/C genotype expressed higher levels of TLR4 on their surfaces than those from subjects with the other genotypes. Peripheral blood mononuclear cells (PBMCs) from the C/C and G/C subjects secreted higher levels of IL-8 in response to lipopolysaccharide (LPS), a TLR4 ligand, than the cells from the G/G subjects. However, there was no significant difference in TLR4 mRNA levels in PBMCs from the subjects with each genotype. After stimulation with tripalmitoylated CSK(4) (Pam(3)CSK(4)), TLR4 mRNA levels increased in PBMCs from both the C/C and G/G subjects, whereas TLR4 protein levels increased in PBMCs from the C/C but not G/G subjects. Transient transfection of a series of chimeric luciferase constructs revealed that a fragment of 3'-UTR containing rs11536889 G allele, but not C allele, suppressed luciferase activity induced by LPS or IL-6. Two microRNAs, hsa-miR-1236 and hsa-miR-642a, were predicted to bind to rs11536889 G allele. Inhibition of these microRNAs reversed the suppressed luciferase activity. These microRNA inhibitors also up-regulated endogenous TLR4 protein on THP-1 cells (the G/G genotype) after LPS stimulation. Furthermore, mutant microRNAs that bind to the C allele inhibited the luciferase activity of the construct containing the C allele. These results indicate that genetic variation of rs11536889 contributes to translational regulation of TLR4, possibly by binding to microRNAs.

Asymmetric Cycloadditions of Acyclic Carbonyl Ylides with Aldehydes Catalyzed by a Chiral Binaphthyldiimine-Ni(II) Complex: Enantioselective Synthesis of 1,3-Dioxolanes and Mechanistic Studies by DFT Calculations.

Chiral binaphthyldiimine-Ni(II)-catalyzed asymmetric 1,3-dipolar cycloaddition reactions between acyclic carbonyl ylides generated from donor-acceptor oxiranes and aldehydes are reported. Both aromatic and aliphatic aldehydes could be used as dipolarophiles, providing cis-1,3-dioxolanes with high diastereo- and enantioselectivities. On the basis of mechanistic studies, a monomeric chiral Ni(II) complex was hypothesized to act as the active species for the cycloaddition. The high levels of asymmetric induction are satisfactorily explained by a concerted-asynchronous endo Si-face approach of the aldehyde.

Analysis of Subgingival Plaque Ability to Stimulate Toll-Like Receptor 2 and 4.

BACKGROUND: It has been shown that toll-like receptor (TLR) 2- and TLR4-stimulating abilities of supragingival plaque (SPP) are associated with periodontal conditions. It is hypothesized that SPP might affect the periodontium through its influence on subgingival plaque (SBP). This study investigates relationships between TLR2- and TLR4-stimulating abilities of SBP and periodontal conditions. METHODS: One hundred thirteen SBP samples were collected from the deepest pockets in patients with chronic periodontitis. TLR2- and TLR4-stimulating abilities were measured using genetically engineered nuclear factor-kappa B reporter cells. Numbers of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in each plaque sample were determined by real-time polymerase chain reaction. Peripheral blood mononuclear cells (PBMCs) were stimulated with SBP samples in presence or absence of TLR4 or TLR2 inhibitor. Production of tumor necrosis factor (TNF)-α and interleukin (IL)-8 was analyzed by enzyme-linked immunosorbent assay. RESULTS: TLR4-stimulating ability of SBP was associated with plaque index (PI), but not with other clinical parameters at sampling sites. TLR2-stimulating ability of SBP was associated with none of the parameters. Number of P. gingivalis and A. actinomycetemcomitans in each plaque sample was not associated with TLR2- or TLR4-stimulating ability of SBP. PBMCs stimulated with SBP samples produced TNF-α and IL-8, which was inhibited by TLR4 but not by TLR2 inhibitor. CONCLUSION: TLR4- but not TLR2-stimulating ability of SBP is associated with PI. Enhanced TLR4-stimulating ability at sites with accumulated plaque may mediate gingival inflammation.

An orthodontic case of transposition of the upper right canine and first premolar.

Tooth transposition is a rare and severe positional anomaly that may create many orthodontic problems from both esthetic and functional points of view. In this report, we describe a case of the orthodontic management of a transposition of the upper canine and premolar with congenital absence of the upper lateral incisor. The patient was treated with a multibracket appliance and the extraction of three premolars, and treatment was completed without a need for any prosthetic replacement.