Clinical effect of equol supplementation in the treatment of desquamative gingivitis with 1-year follow-up.

PURPOSE: Desquamative gingivitis (DG) is characterized by desquamative erosion, edematous erythema, and vesicle formation on the gingiva. Because of its prevalence in women during the pre- and postmenopausal period, its potential association with female hormones has been suggested. Equol is a soy isoflavone metabolite with a chemical structure similar to estrogen. Scientific evidence suggests that equol helps in alleviating menopausal symptoms. This study evaluated the clinical effect of a 12-month equol supplementation as a substitute for estrogen to alleviate DG symptoms. METHODS: The study enrolled 16 women with DG who regularly visited Nihon University School of Dentistry Dental Hospital. Urinary equol levels, periodontal tissue examination, O'Leary's plaque control record, stimulated saliva flow rate, and gingival pain-related questionnaires were evaluated before and after the 12-month daily intake of 10 mg equol supplement. RESULTS: Equol supplementation led to a statistically significant improvement in bleeding on probing, visual findings, and reductions in the frequency and severity of gingival pain. CONCLUSION: Urinary equol testing and equol supplementation may be novel treatment options for female patients with DG.

Knockdown of TFAP2E results in rapid G2/M transition in oral squamous cell carcinoma cells.

TFAP2E is a member of the activator protein-2 transcription factor family and acts as a tumor suppressor in several types of cancer. Downregulation of TFAP2E expression is significantly associated with a shorter overall survival period in patients with oral squamous cell carcinoma (OSCC). To evaluate the molecular mechanisms by which TFAP2E suppresses the development or progression of OSCC, the present study investigated the effects of TFAP2E downregulation on OSCC-derived Ca9-22 and HSC-4 cells. The present study demonstrated that small interfering RNA mediated-knockdown of TFAP2E accelerated the proliferation of these OSCC cell lines compared with that in the control group, as determined by the standard water-soluble tetrazolium salt-8 assay. To analyze the cell cycle progression rate, the cell cycle distribution patterns of TFAP2E-knockdown and control cells cultured in the presence of nocodazole, which prevents the completion of mitosis, were analyzed by fluorescence-activated cell sorting at different time points. When analyzing cellular DNA contents, no major differences in cell cycle profiles were observed; however, the rate of increase in cells positive for histone H3 Serine 28 phosphorylation, a standard molecular marker of early M phase, was significantly higher in TFAP2E-knockdown cells than in the control cells. Collectively, these results suggested that TFAP2E may attenuate the proliferation of OSCC cells by regulating G2/M transition.

Resorbable bilayer membrane made of L-lactide-ε-caprolactone in guided bone regeneration: an in vivo experimental study.

PURPOSE: Guided bone regeneration (GBR) is an accepted method in dental practice that can successfully increase the bone volume of the host at sites chosen for implant placement; however, existing GBR membranes exhibit rapid absorption and lack of adequate space maintenance capabilities. We aimed to compare the effectiveness of a newly developed resorbable bilayer membrane composed of poly (L-lactic acid) and poly (-caprolactone) (PLACL) with that of a collagen membrane in a rat GBR model. METHODS: The rat calvaria was used as an experimental model, in which a plastic cylinder was placed. We operated on 40 male Fisher rats and subsequently performed micro-computed tomography and histomorphometric analyses to assess bone regeneration. RESULTS: Significant bone regeneration was observed, which was and similar across all the experimental groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, and sporadic partial degradation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. CONCLUSIONS: The PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane could address the limitations of the current membranes. Nevertheless, further studies and clinical trials are warranted to validate the efficacy and safety of The PLACL membrane in humans.

Fusobacterium nucleatum putatively affects the alveoli by disrupting the alveolar epithelial cell tight junction, enlarging the alveolar space, and increasing paracellular permeability.

Fusobacterium nucleatum (Fn) is abundant in the human oral cavity and has been associated with periodontal disease, which in-turn has been linked to respiratory disease development. Tight junctions (TJs) line the airway and alveoli surfaces serving as a first line of defense against multiple pathogens. Fn has already been linked to respiratory diseases, however, how Fn affects the alveolar TJ was not fully elucidated. Here, we designed and analyzed a TJ network, grew Fn cells and inoculated it in vitro (16HBE and primary cells) and in vivo (mice lung), measured transepithelial electrical resistance, performed RT-PCR, checked for in vitro cell and mice lung permeability, and determined air space size through morphometric measurements. We found that Fn can potentially affect TJs proteins that are directly exposed to the alveolar surface. Additionally, Fn could possibly cause neutrophil accumulation and an increase in alveolar space. Moreover, Fn putatively may cause an increase in paracellular permeability in the alveoli.

Association Between Olfactory Test Data with Multiple Levels of Odor Intensity and Suspected Cognitive Impairment: A Cross-Sectional Study.

BACKGROUND: Olfactory function decline has recently been reported to be associated with a risk of cognitive impairment. Few population-based studies have included younger adults when examining the association between olfactory test data with multiple odor intensities and suspected cognitive impairment. OBJECTIVE: We investigated the association between high-resolution olfactory test data with fewer odors and suspected cognitive impairments. We also examined the differences between older and younger adults in this association. METHODS: The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was administered to 1,450 participants, with three odor-intensity-level olfactometry using six different odors. Logistic regressions to discriminate suspected cognitive impairment were conducted to examine the association, adjusted for age, sex, education duration, and smoking history. Data were collected from the Program by Tohoku University Tohoku Medical Megabank Organization, with an additional olfactory test conducted between 2019 and 2021. RESULTS: We generally observed that the lower the limit of distinguishable odor intensity was, the higher the MoCA-J score was. The combination of spearmint and stuffy socks contributed most to the distinction between suspected and unsuspected cognitive impairment. Furthermore, the association was significant in women aged 60-74 years (adjusted odds ratio 0.881, 95% confidence interval [0.790, 0.983], p = 0.024). CONCLUSIONS: The results indicate an association between the limit of distinguishable odor intensity and cognitive function. The olfactory test with multiple odor intensity levels using fewer odors may be applicable for the early detection of mild cognitive impairment, especially in older women aged 60-74 years.

Co-Stimulation of AGEs and LPS Induces Inflammatory Mediators through PLCγ1/JNK/NF-κB Pathway in MC3T3-E1 Cells.

Advanced glycation end-products (AGEs) are increased under hyperglycemia in vivo and are associated with the onset of diabetes. According to previous studies, AGEs exacerbate inflammatory diseases. However, the mechanism by which AGEs aggravate osteoblast inflammation remains unknown. Therefore, the aim of this study was to determine the effects of AGEs on the production of inflammatory mediators in MC3T3-E1 cells and the underlying molecular mechanisms. Co-stimulation with AGEs and lipopolysaccharide (LPS) was found to increase the mRNA and protein levels of cyclooxygenase 2 (COX2), interleukin-1α (IL-1α), S100 calcium-binding protein A9 (S100A9), and the production of prostaglandin E2 (PGE2) compared to no stimulation (untreated control) or individual stimulation with LPS or AGEs. In contrast, the phospholipase C (PLC) inhibitor, U73122, inhibited these stimulatory effects. Co-stimulation with AGEs and LPS also increased the nuclear translocation of nuclear factor-kappa B (NF-κB) compared to no stimulation (untreated control) or individual stimulation with LPS or AGE. However, this increase was inhibited by U73122. Co-stimulation with AGEs and LPS-induced phosphorylated phospholipase Cγ1 (p-PLCγ1) and phosphorylated c-Jun N-terminal kinase (p-JNK) expression compared to no stimulation or individual stimulation with LPS or AGEs. U73122 inhibited the effects induced by co-stimulation. siPLCγ1 did not increase the expression of p-JNK and the translocation of NF-κB. Overall, co-stimulation with AGEs and LPS may promote inflammation mediators in MC3T3-E1 cells by activating the nuclear translocation of NF-κB via PLCγ1-JNK activation.

Visualization of estimated prevalence of CES-D positivity accounting for background factors and AIS scores.

Development of methods for population screening is necessary to improve the efficiency of secondary prevention of diseases. Until now, a common cutoff has been used for all people in the data set. However, if big data for health information can be used to modify individual cutoffs according to background factors, it may avoid wasting medical resources. Here we show that the estimated prevalence of the Center for Epidemiologic Studies Depression Scale positivity can be visualized by a heatmap using background factors from epidemiological big data and scores from the Athens Insomnia Scale. We also show that cutoffs based on the estimated prevalence can be used to decrease the number of people screened without decreasing the number of prevalent cases detected. Since this method can be applied to the screening of different outcomes, we believe our work can contribute to the development of efficient screening methods for various diseases.

Machine Learning in Predicting Tooth Loss: A Systematic Review and Risk of Bias Assessment.

Predicting tooth loss is a persistent clinical challenge in the 21st century. While an emerging field in dentistry, computational solutions that employ machine learning are promising for enhancing clinical outcomes, including the chairside prognostication of tooth loss. We aimed to evaluate the risk of bias in prognostic prediction models of tooth loss that use machine learning. To do this, literature was searched in two electronic databases (MEDLINE via PubMed; Google Scholar) for studies that reported the accuracy or area under the curve (AUC) of prediction models. AUC measures the entire two-dimensional area underneath the entire receiver operating characteristic (ROC) curves. AUC provides an aggregate measure of performance across all possible classification thresholds. Although both development and validation were included in this review, studies that did not assess the accuracy or validation of boosting models (AdaBoosting, Gradient-boosting decision tree, XGBoost, LightGBM, CatBoost) were excluded. Five studies met criteria for inclusion and revealed high accuracy; however, models displayed a high risk of bias. Importantly, patient-level assessments combined with socioeconomic predictors performed better than clinical predictors alone. While there are current limitations, machine-learning-assisted models for tooth loss may enhance prognostication accuracy in combination with clinical and patient metadata in the future.

Classification of Southeast Asian mints (Mentha spp.) based on simple sequence repeat markers.

Mentha is a complex genus encompassing many species as a consequence of their interspecific hybridization and polyploidy. Southeast Asian mints have been poorly distinguished though they are widely used for culinary and medical purposes. In this study, we have analyzed Southeast Asian mints and known varieties as well as a related Lamiaceae species (Nepeta sp.) using simple sequence repeat (SSR) markers and leaf morphology. Two types of mints were clearly distinguished based on their venation pattern and leaf shape index. We developed 12 SSR markers that allowed good amplification in the Mentha and another Lamiaceae species. In the SSR-based phylogram, the Mentha lines could be delimited into groups I-VI. The Southeast Asian mints divided into groups I and II, and the phylogram separated most of the available species, with groups I and II containing the known species M. × cordifolia and M. arvensis, respectively. The separation of the two groups was supported by a population structure analysis. The SSR markers developed in this study enabled the simultaneous classification of mints and will help improve our understanding of the genetic composition of known mint varieties and as yet unclassified Southeast Asian mints.

Switching to tenofovir alafenamide versus continued therapy in chronic hepatitis B patients who were treated with entecavir: A prospective, multicenter, randomized controlled study.

BACKGROUNDS: Entecavir (ETV) and tenofovir alafenamide fumarate (TAF) have been used widely to treat patients with chronic hepatitis B virus (HBV) infection, but it is still unclear how best to use these drugs. Although some studies compared the efficacies of treatment switch from ETV to TAF, there has been no randomized study. METHODS: We performed a prospective multicenter randomized controlled study in which subjects were enrolled from April 2018 to June 2019 and observed for 2 years until March 2021 to clarify the efficacy and safety of switching from ETV to TAF. RESULTS: Thirty-three patients were enrolled and randomized into 2 groups, and a total of 30 patients were evaluated; a TAF-switching group (n = 16) and an ETV-continuing group (n = 14). The mean age of the 30 patients was 61 years old and 18 patients (60%) were male. The serum HBV DNA in all patients were below detection limit. The mean change in hepatitis B surface antigen (HBsAg) levels after 2 years was not significantly different between the TAF and ETV groups (-0.08 vs -0.20 log IU/mL, P = .07). Comparing the group with a HBsAg decline (≤ -0.1 log IU/mL) and a group without a HBsAg decline in an overall analysis, the prior ETV duration was significantly shorter in the HBsAg-declined group (49 vs 92 months, P = .03). Although the eGFR levels tended to decrease in the TAF group compared to ETV (-6.15 vs -2.26 mL/min/1.73 m2, P = .09), no significant differences were observed in patients with baseline eGFR < 60 (-2.49 vs 0.40 mL/min/1.73 m2, P = .25). CONCLUSION: The efficacy and safety were comparable in the TAF-switching group and the ETV-continuing group. Because the present study was conducted in limited patients, a larger study will be required.

Mild elevation of C-reactive protein in a young patient with severe periodontitis: a case report with 2 years of follow-up.

Periodontal inflammation is associated with systemic disease. Low-grade inflammation (LGI) is critical to the link between periodontal disease and several systemic disorders. C-reactive protein (CRP) is a common circulating biomarker for acute-phase immune responses, and it is closely related to LGI. The present case demonstrated excellent results using a comprehensive approach for periodontitis in a young woman with severe periodontitis and mild CRP elevation. A 21-year-old Japanese woman complained of tooth mobility and bleeding during tooth brushing. She was pre-obese (body mass index = 29.9), and she had a mildly elevated CRP level (5.2 mg/L). Of all periodontal sites, 34.5% had deep pockets (≥6 mm). The patient was diagnosed with stage III, grade C periodontitis and generalized aggressive periodontitis. Comprehensive periodontal treatments, including regenerative procedures for vertical bone loss and furcation involvement, were performed. Periodontal tissue inflammation was resolved, and periodontal regeneration was achieved. During the 2-year follow-up period, her teeth did not exhibit any signs of instability, attachment loss, or bone loss. Despite the weak nature of the evidence, this case suggests that CRP is valuable for assessing LGI, and it may potentially be considered during periodontal grading in the future.

Cumulative risk of developing a new symptom in patients with primary biliary cholangitis and its impact on prognosis.

Background and Aim: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

Combinational elastography for assessment of liver fibrosis in patients with liver injury.

OBJECTIVE: We investigated the utility of combinational elastography with point shear wave elastography (pSWE) and real-time tissue elastography (RTE) for evaluating liver fibrosis in patients with liver injury. METHODS: In this prospective single-institution study, patients scheduled for a liver biopsy to determine the presence of liver disease were enrolled. Liver fibrosis in each patient was evaluated using both shear wave velocity (Vs) shown by pSWE and the liver fibrosis index (LFI) shown by RTE, while a liver biopsy sample was obtained from the same area that was subjected to an elastography examination. Results of the latter were compared with those obtained in a histological examination. RESULTS: Multivariate analysis showed that Vs and LFI were significantly correlated with the liver fibrosis stage in all of the enrolled patients. Sub-analysis findings compared patients with and without non-alcoholic fatty liver disease (NAFLD) and demonstrated that Vs was significantly correlated with the liver fibrosis stage in both groups, whereas LFI was correlated with that only in the non-NAFLD patients. However, a multivariate analysis demonstrated a significant correlation between steatosis grade and LFI in the NAFLD patients. CONCLUSIONS: RTE is less useful than pSWE for assessing liver fibrosis in patients with NAFLD.

Efficacy of endoscopic gallbladder drainage in patients with acute cholecystitis.

BACKGROUND: Early cholecystectomy is recommended for patients with acute cholecystitis. However, emergency surgery may not be indicated due to complications and disease severity. Patients requiring drainage are usually treated with percutaneous transhepatic gallbladder drainage (PTGBD), whereas patients with biliary duct stones undergo endoscopic stones removal followed by endoscopic gallbladder drainage (EGBD). Herein, we investigated the efficacy of EGBD in patients with acute cholecystitis. METHODS: Overall, 101 patients receiving laparoscopic cholecystectomy between September 2019 and September 2020 in our department were retrospectively analyzed. RESULTS: The patients (n = 101) were divided into three groups: control group that did not undergo drainage (n = 68), a group that underwent EGBD (n = 7), and a group that underwent PTGBD (n = 26). Median surgery time was 107, 166, and 143 min, respectively. Control group had a significantly shorter surgery time, whereas it did not significantly differ between EGBD and PTGBD groups. The median amount of bleeding was 5 g, 7 g, and 7.5 g, respectively, and control group had significantly less bleeding than the drainage group. We further divided patients into the following subgroups: patients requiring a 5 mm clip to ligate the cystic duct, patients requiring a 10 mm clip due to the thickness of the cystic duct, patients requiring an automatic suturing device, and patients undergoing subtotal cholecystectomy due to impossible cystic duct ligation. There was no significant difference between EGBD and PTGBD regarding the clip used or the need for an automatic suturing device and subtotal cholecystectomy. CONCLUSIONS: There was no significant difference between EGBD and PTGBD groups regarding surgery time or bleeding amount when surgery was performed after gallbladder drainage for acute cholecystitis. Therefore, EGBD was considered a useful preoperative drainage method requiring no drainage bag.

A 15-year Follow-Up of a Gingivectomy Procedure for Idiopathic Gingival Fibromatosis: A Case Report and Literature Review.

Few long-term reports exist concerning the treatment of idiopathic gingival fibromatosis, which is a rare autosomal dominant genetic disorder associated with non-inflammatory, benign, and chronic fibrous gingival proliferation and which causes serious esthetic problems. The aim of this study was to report a case of idiopathic gingival fibromatosis treated with a gingivectomy using an inverse bevel flap method and comprehensively followed up for 15 years. A female patient visited a pediatric dentist at 7 years of age; however, a gingivectomy was not performed until the age of 20 years because of an uncertain prognosis. Now, more than 15 years after the gingivectomy, there has been no significant recurrence and the disease is well managed. Treatment by gingivectomy with an inverse bevel flap approach may provide long-term prevention of recurrence of gingival fibromatosis into adulthood. The aim of this study was to obtain new findings on the pathogenesis and prognosis of this rare disease and to review the case reports previously published.

Magnetically Manipulable Ionic Liquid Crystals Incorporating Neutral Radicals.

Invited for this month's cover are the collaborating groups of Dr. Yoshiaki Uchida from Osaka University, Japan, Prof. Rui Tamura and Prof. Masahito Sugiyama from Kyoto University, Japan and Dr. Dmitrii G. Mazhukin from Novosibirsk State University, Russia. The cover picture depicts a contrast between localized spins and conductive ions in the newly-synthesized ionic liquid crystalline (ILC) nitroxide radicals. The ILC droplet of the new compounds is magnetically manipulable. More information can be found in the Full Paper by Yoshiaki Uchida, Rui Tamura, and co-workers.

Two-year administration of sodium-glucose co-transporter 2 inhibitor brought about marked reduction of body fat independent of skeletal muscle amount or glycemic improvement in Japanese patients with type 2 diabetes.

AIM: To investigate long-term effects of sodium-glucose co-transporter 2 inhibitor (SGLT2i) on anthropometric and metabolic factors in Japanese patients with type 2 diabetes (T2DM). PATIENTS AND METHODS: This is a retrospective observation study. Forty-six outpatients with T2DM (32 men and 14 women, 51 ± 13 years old, BMI 27.9 ± 4.8, means ± S.D.) who had been treated by SGLT2i for 2 years were selected and their metabolic and anthropometric data were retrieved from medical records retrospectively. Regular instruction for diet and exercise had been performed throughout the administration of SGLT2i in outpatient clinic basis. RESULTS: By the administration of SGLT2i for 2 years, body weight and body fat amount were significantly reduced (P < 0.0001) in spite of no change in skeletal muscle mass. HbA1c (P < 0.0001), liver function and lipid profile (P < 0.01) were ameliorated and eGFR was reduced significantly (P < 0.0001). It is of note that the reduction of body weight was strongly correlated to that of body fat (r = 0.951, P < 0.0001) with no correlation to the change of skeletal muscle mass. The reduction of HbA1c was strongly correlated to the baseline HbA1c (r = - 0.922, P < 0.0001) and modestly correlated to the baseline eGFR (r = - 0.449, P < 0.01). Multivariate analysis revealed a weak relationship between the amelioration of HbA1c and the reduction of body weight. CONCLUSION: SGLT2i can effectively reduce body weight and body fat mass independent of the blood glucose improvement or the renal function. Under the periodical instruction for nutrition and exercise this oral hypoglycemic agent can be safely administered for a long term without a risk for sarcopenia.

Epstein-Barr Virus Promotes the Production of Inflammatory Cytokines in Gingival Fibroblasts and RANKL-Induced Osteoclast Differentiation in RAW264.7 Cells.

Periodontitis is an inflammatory condition that causes the destruction of the supporting tissues of teeth and is a major public health problem affecting more than half of the adult population worldwide. Recently, members of the herpes virus family, such as the Epstein-Barr virus (EBV), have been suggested to be involved in the etiology of periodontitis because bacterial activity alone does not adequately explain the clinical characteristics of periodontitis. However, the role of EBV in the etiology of periodontitis is unknown. This study aimed to examine the effect of inactivated EBV on the expression of inflammatory cytokines in human gingival fibroblasts (HGFs) and the induction of osteoclast differentiation. We found that extremely high levels of interleukin (IL)-6 and IL-8 were induced by inactivated EBV in a copy-dependent manner in HGFs. The levels of IL-6 and IL-8 in HGFs were higher when the cells were treated with EBV than when treated with lipopolysaccharide and lipoteichoic acid. EBV induced IκBα degradation, NF-κB transcription, and RAW264.7 cell differentiation into osteoclast-like cells. These findings suggest that even without infecting the cells, EBV contributes to inflammatory cytokine production and osteoclast differentiation by contact with oral cells or macrophage lineage, resulting in periodontitis onset and progression.

Butyric acid modulates periodontal nociception in Porphyromonas gingivalis-induced periodontitis.

PURPOSE: Periodontitis progresses with chronic inflammation, without periodontal pain. However, the underlying mechanisms are not well known. Here, the involvement of butyric acid (BA) in periodontal pain sensitivity in Porphyromonas gingivalis (P. gingivalis)-induced periodontitis was examined. METHODS: P. gingivalis was inoculated into the ligature which was tied around the molar (P. gingivalis-L) and the gingival mechanical head withdrawal threshold (MHWT) was measured. Following P. gingivalis-L, the expressions of orphan G protein-coupled receptor 41 (GPR41) in trigeminal ganglion (TG) neurons were examined. The amount of gingival BA was analyzed following the P. gingivalis-L and the changes in the MHWT in complete Freund's adjuvant (CFA)-injected gingival tissue by gingival BA were examined. The changes in the MHWT following P. gingivalis-L by gingival GPR41 antagonist (HA) were examined. RESULTS: No change in the MHWT was observed, GPR41-immunoreactive TG neurons were increased following P. gingivalis-L. The gingival BA amount increased following P. gingivalis-L, and the gingival BA suppressed the decrease in MHWT following CFA. HA decreased MHWT following P. gingivalis-L. CONCLUSION: Gingival BA modulates periodontal mechanical nociception via GPR41 signaling in P. gingivalis-L-induced periodontitis.