Three-year outcomes of preoperative chemoradiotherapy plus nivolumab in microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). We reported the short-term outcomes of the VOLTAGE trial that investigated the safety and efficacy of preoperative CRT followed by nivolumab and surgery. Here, we present the 3-year outcomes of this trial. METHODS: Thirty-nine patients with microsatellite stable (MSS) LARC and five patients with microsatellite instability-high (MSI-H) LARC underwent CRT (50.4 Gy) followed by five doses of nivolumab (240 mg) and surgery. The 3-year relapse-free survival (RFS), overall survival (OS), and associations with biomarkers were evaluated. RESULTS: The 3-year RFS rates in patients with MSS and MSI-H were 79.5% and 100%, respectively, and the 3-year OS rates were 97.4% and 100%, respectively. Of the MSS patients, those with pre-CRT PD-L1 positivity, pre-CRT high CD8 + T cell/effector regulatory T cell (eTreg) ratio, pre-CRT high expression of Ki-67, CTLA-4, and PD-1 had a trend toward better 3-year RFS than those without. CONCLUSIONS: Three-year outcomes of patients with MSI-H were better than those of patients with MSS. PD-L1 positivity, elevated CD8/eTreg ratio, and high expression of Ki-67, CTLA-4, and PD-1 could be positive predictors of prognosis in patients with MSS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02948348.

Hip-sacroiliac joint-spine syndrome in total hip arthroplasty patients.

This study is designed to compare the extent of sacroiliac joint (SIJ) degeneration at total hip arthroplasty (THA) for two pathologies: osteoarthritis of the hip (OA) and osteonecrosis of the femoral head (ON). We also assessed the prevalence of SIJ degeneration in patients with lumbar spondylolisthesis or degenerative scoliosis. A total of 138 hips from 138 patients (69 OA and 69 ON) were assessed in this study, including 66 hips affected by OA secondary to developmental dysplasia of the hip. The degenerative changes in the SIJ and lumbar spine were evaluated prior to THA using radiographs and computed tomography (CT) scans, showing 9 instances of spondylolisthesis and 38 of degenerative scoliosis. The OA group exhibited longer duration from onset to surgery than the ON group. The OA group also included more cases with significant pelvic obliquity (3 degrees or more) and with significant increases in SIJ sclerosis and irregularities. Patients with lumbar spondylolisthesis or degenerative scoliosis were significantly more likely to have SIJ irregularities. The prevalence of SIJ degeneration was higher in cases of THA for OA than for ON. This study also suggests the possibility of Hip-SIJ-Spine syndrome in THA patients with OA.

Mitigation of paclitaxel-induced peripheral neuropathy in breast cancer patients using limb-cooling apparatus: a study protocol for a randomized controlled trial.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment. Methods: This study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation. Discussion: The results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic. Clinical trial registration: https://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.

Comparative Study of Highly Cross-Linked Polyethylene Liner Wear by Hip Center Location Using Elevated Hip Center Technique in Crowe I to III Hip Dysplasia: Outcomes for a Minimum of Eighteen Years of Follow-Up.

BACKGROUND: The literature has reported that supero-lateralization of the femoral head increases the rates of aseptic loosening and prosthesis revision. However, there are few reports on the influence of different hip center positions on liner wear with more than a 15-year follow-up period. METHODS: From April 2000 to August 2003, 91 patients underwent 108 total hip arthroplasties using a highly cross-linked polyethylene liner combined with zirconia femoral head and cup components. Pelvic radiographs were used to assess the vertical and horizontal distances to the center of the hip and the amount of liner wear. Mean patient age at the time of surgery was 54 years (range, 33 to 73), and mean follow-up duration was 19 years (range, 18 to 21). RESULTS: Average liner wear was 0.221 mm, with average annual wear of 0.012 mm/year. Mean vertical and horizontal distances for the hip center were 24.9 and 31.8 mm, respectively. There was no difference in linear wear between patients who had different hip center heights (<20, 20 to 30, and >30 mm), and quadrant partitioning showed no differences across the 4 quadrant zones. CONCLUSION: At a minimum of 18 years of follow-up in patients having developmental dysplasia of the hip who had different Crowe subtypes and different hip centers, elevated hip center and uncemented fixation techniques using a highly cross-linked polyethylene on ceramic components were associated with very low wear rates and excellent functional scores.

Collarless Polished Tapered Stems of Identical Shape Provide Differing Outcomes for Stainless Steel and Cobalt Chrome: A Biomechanical Study.

Cemented polished tapered femoral stems (PTS) made of cobalt-chrome alloy (CoCr) are a known risk factor for periprosthetic fracture (PPF). The mechanical differences between CoCr-PTS and stainless-steel (SUS) PTS were investigated. CoCr stems having the same shape and surface roughness as the SUS Exeter® stem were manufactured and dynamic loading tests were performed on three each. Stem subsidence and the compressive force at the bone-cement interface were recorded. Tantalum balls were injected into the cement, and their movement was tracked to indicate cement movement. Stem motions in the cement were greater for the CoCr stems than for the SUS stems. In addition, although we found a significant positive correlation between stem subsidence and compressive force in all stems, CoCr stems generated a compressive force over three times higher than SUS stems at the bone-cement interface with the same stem subsidence (p < 0.01). The final stem subsidence amount and final force were greater in the CoCr group (p < 0.01), and the ratio of tantalum ball vertical distance to stem subsidence was significantly smaller for CoCr than for SUS (p < 0.01). CoCr stems appear to move more easily in cement than SUS stems, which might contribute to the increased occurrence of PPF with the use of CoCr-PTS.

Factors associated with diabetes control : results of a 2-year cohort study of outpatients with type 2 diabetes.

Type 2 diabetes is a typical lifestyle disease. We aimed to identify the factors affecting glycemic control in 64 outpatients with type 2 diabetes over a 2-year period. We defined poor glycemic control using a change in glycosylated hemoglobin (?HbA1c) of ??0.5% over 2 years and/or HbA1c ??7.5% at the end of the study period. We used a questionnaire to collect information on oral health behavior and lifestyle, including eating and smoking habits, and analyzed the relationships between indices of diabetes control and responses to the questionnaire. The mean (SD) HbA1c of the participants was 6.87% (0.77%) at a baseline, and 6.93% (0.69%) after 2 years. Twenty-three participants (36.0%) had poor glycemic control. ?HbA1c and the change in body mass index (?BMI) correlated (Spearman's rank correlation, r?=?0.350, p?

The relationship between subjective oral frailty and adverse health outcomes or medical and dental expenditures in the latter-stage older adult: A 6-year longitudinal study.

OBJECTIVES: The study aimed to investigate the relationship between subjective oral frailty and adverse health outcomes or medical and dental expenditures in the latter-stage older adult through a 6-year longitudinal study. METHODS: The participants enrolled in the cross-sectional study were 3564 Tokushima City residents aged 75, 80, 85, and 90 years old who received oral health examinations and who responded to a questionnaire on oral conditions and health behavior at baseline. The data for the occurrence of disability or mortality, and the monthly medical expenditures, dental expenditures, and total medical expenditure of each participant were obtained from the National Health Insurance Database. RESULTS: The total medical expenditure showed significant differences in participants who had difficulties in eating tough foods, difficulties in swallowing tea or soup, and dry mouth when compared to that of healthy participants, in addition to the current medical treatment against the general disease. The 6-year longitudinal study revealed that participants with subjective oral frailty symptoms, including difficulties in eating tough foods and difficulties in swallowing tea or soup at baseline, had significantly higher medical, dental, and total expenditures among 538 participants without certified nursing care. In addition, those with subjective oral frailty or with less than 19 teeth present were shown to have a higher possibility for the occurrence of disability or mortality by the cox proportional hazard analysis. Furthermore, it was found that medical and total expenditures in older adults with adverse health outcomes were higher than that of healthy participants. CONCLUSION: These results suggest that subjective oral frailty in the latter-stage older adult is related to subsequent adverse health outcomes and an increase in medical and dental expenditures.

Angular changes in pelvic tilt and cup orientation at a minimum of eighteen years after primary total hip arthroplasty with an uncemented cup.

BACKGROUND: Changes in pelvic tilt angle (PTA) and cup orientation have been reported in patients after total hip arthroplasty, but the current literature generally has a brief follow-up period. This study will be the first to report PTA and cup orientation changes in the supine position for a minimum 18 years after total hip arthroplasty (THA) and investigate the factors associated with pelvic tilt and cup orientation changes. METHODS: In this study, 101 patients (120 hips) who underwent THA were retrospectively analyzed. The aims of our study were to evaluate the PTA and cup orientation change over 18 years after THA to assess differential PTA, cup inclination, and anteversion. We also investigated whether factors such as gender, body mass index, and age have any influence on PTA and cup orientation after THA. RESULTS: Patients showed a significant incremental change in PTA pre-operatively, immediately post-operatively, and at final follow-up. Cup orientation increased significantly at the final follow-up compared to the immediate post-operative period. Gender subgroup analysis showed that PTA was significantly greater in females than in males at the final follow-up (p = 0.025). Age subgroup analysis showed that PTA was significantly greater in the over 60 years group than in the other groups. CONCLUSION: Our patients showed significant changes in PTA and cup orientation at a minimum 18 years after surgery, especially in females over 60 years. Female patients over 60 are a risk factor after THA.

Does the Dual Mobility Cup Reduce Dislocation After Primary Total Hip Arthroplasty in Elderly Patients at High Risk of Dislocation?

OBJECTIVE: The dual mobility cup (DMC) is designed to extend the longevity of the prosthesis by improving stability, enhancing the range of motion, and decreasing impingement without increasing wear. We hypothesized that DMC would reduce the risk of dislocation in elderly patients. This study aimed to investigate the clinical and radiographic outcomes of DMC-total hip arthroplasty (THA) in elderly patients at high risk of dislocation. METHODS: From June 2016 to March 2020, 94 patients with a mean age of 77.7 years (97 hips) who underwent a posterolateral approach for DMC-THA in our department were followed up for at least one year. Preoperative and postoperative pelvic tilt angles (PTA) and DMC orientation were prospectively collected for all patients. Intraoperative and postoperative complications were recorded. A parametric test was used for normal distribution, and a non-parametric test was used for non-normal distribution. RESULTS: Abduction and anteversion angles of the cup were 42.4 and 18.0° in the supine position immediately postoperative. The average PTA for patients in the supine and standing positions were 26.5 and 34.5°, respectively. When moving from the supine to the standing position, patients experienced a mean posterior pelvic tilt of 9°. No intraoperative acetabular-related complications were recorded. Postoperative complications included early infection in one patient (1.0%) and dislocation in one patient (1.0%). CONCLUSION: Our study demonstrates that DMC-THA provides satisfactory short-term outcomes in elderly patients at a high risk of dislocation, regardless of the change in PTA resulting from postural transition.

Oral care tablet containing kiwifruit powder affects tongue coating microbiome.

OBJECTIVES: Tongue coating, a kind of biofilm formed on the tongue dorsum, is the cause of various clinical conditions, such as oral halitosis and periodontal diseases, because Fusobacterium nucleatum acts as a bridge between other oral bacteria and periodontopathogenic bacteria in biofilm formation. Our previous clinical study revealed that taking oral care tablets containing kiwifruit powder significantly reduced not only tongue-coating index and volatile sulfur compounds but also total bacteria and F. nucleatum in tongue coating. In this study, we analyzed the microbiome of tongue coating samples obtained before and after oral care tablets intake to clarify whether this tablet is a useful tool for daily tongue care. METHODS: Thirty-two healthy young adults were enrolled, and a crossover clinical trial was conducted. We instructed subjects to remove tongue coating by tongue brush for intervention I, to keep the oral care tablet containing kiwifruit powder on the tongue dorsum and to let it dissolve naturally for intervention II. Microbial DNA was isolated from the collected tongue coating samples in each subject, then 16S rRNA next-generation sequencing, operational taxonomic unit clustering, and statistical analysis were performed. RESULTS: The microbiome analysis revealed that the oral care tablet in intervention II prompted a significant change in the tongue microbiota composition, a significant reduction in the relative abundance of Prevotella and Porphyromonas, and an increase in Firmicutes/Bacteroidetes ratio when compared to that in intervention I. CONCLUSION: These results suggested that the oral care tablet might contribute to the improvement of the oral condition due to its good influence on the tongue coating microbiome.

Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) and surgical resection are the standard treatment for locally advanced rectal cancer (LARC). Combining immune checkpoint inhibitors with radiation suggests a promising approach for enhancing efficacy. We investigated the efficacy of CRT followed by nivolumab and surgery in patients with LARC. PATIENTS AND METHODS: In phase I, we investigated the feasibility of sequentially combined CRT, 5 cycles of nivolumab, and radical surgery. In phase II, patients with microsatellite stable (MSS) and microsatellite instability-high (MSI-H) LARC were evaluated. RESULTS: Three patients in phase I received full courses of CRT and nivolumab without dose modification; the schedule was recommended for phase II. A pathologic complete response (pCR) was centrally confirmed in 30% [11/37; 90% confidence interval (CI), 18%-44%] and 60% (3/5) of the MSS and exploratory MSI-H cohorts, respectively. While immune-related severe adverse events were observed in 3 patients, no treatment-related deaths were observed. In 38 patients with MSS who underwent surgery, pCR rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were observed in those with programmed cell death ligand 1 (PD-L1) tumor proportion score ≥1% and <1%, respectively; IHC staining was performed using pre-CRT samples. In 24 patients with MSS, pre-CRT samples were analyzed by flow cytometry; pCR rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) were observed for CD8+ T cell/effector regulatory T cell (CD8/eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating lymphocytes. CONCLUSIONS: CRT followed by consolidation nivolumab could increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio were positive predictors in patients with MSS LARC.

Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial.

The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis ( UMIN000027887 ). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc exploratory analyses revealed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations adjusted for tumor fraction stratified patients according to efficacy with similar accuracy to tissue genotyping. Decreased ctDNA fraction 3 weeks after treatment initiation associated with therapeutic response. Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response. These findings warrant further use of ctDNA genotyping in clinical trials for HER2-amplified mCRC, which might especially benefit patients in first-line treatment.

Bone ingrowth observed in a cup removed during revision surgery for early dislocation after primary THA: A case report.

INTRODUCTION AND IMPORTANCE: Recently cementless total hip arthroplasty (THA) has shown good long-term results with excellent stability resulted from the porous coating of the implant. A hydroxyapatite-tricalcium phosphate (HA-TCP) coating on the porous surface is expected to promote bone ingrowth and to improve initial fixation of the implant. Here we report a case of bone ingrowth observed in a cup removed during revision surgery for early dislocation, 37 days after primary THA using a porous coating cup with HA-TCP. CASE PRESENTATION: A 61-year-old woman who has bilateral osteoarthritis underwent same-day bilateral THA. Both sides used porous coating cups with HA-TCP. Line-to-line technique and screw fixation were utilized. Anterior dislocation of the left hip occurred on days 27 and 31, and we performed cup revision on day 37 after surgery. We noted bone-like tissue on the posterior surface of the cup and in a vacant screw hole. Bone tissue was also confirmed in pathological findings. CLINICAL DISCUSSION: Studies in animals have confirmed early bone ingrowth about 4 weeks after surgery with HA-TCP coated implants. In humans, the earliest report of bone ingrowth in cups is for a cup without HA-TCP coating, detected 5 weeks after surgery. In the present case, we used a porous coating cup with HA-TCP, and bone ingrowth was confirmed at approximately the same time as for the previous case. CONCLUSION: Early clinical bone ingrowth was confirmed in an HA-TCP coated cup, occurring at about the same time after surgery as in previous reports.

Association between diabetes-related clinical indicators and oral health behavior among patients with type 2 diabetes.

Objective : The aim of this study was to evaluate the association between diabetes-related indicators and oral health behavior among patients with type 2 diabetes. Methods : Seventy-four outpatients were included. We administered a questionnaire and divided the patients into two groups according to oral health behavior and eating habits. We then compared diabetes-related clinical records between the groups and performed logistic regression analysis. Results : Participants who brushed their teeth before bedtime every night had lower BMIs than those who did not. Participants who reported eating slowly and chewing well every day had significantly lower HbA1c than their counterparts. Participants who reported gum bleeding had significantly higher LDL-cholesterol than their counterparts. Binominal logistic regression analysis revealed that BMI < 25 was associated with not brushing teeth before bedtime every night, HbA1c < 7.5 with not eating slowly or chewing well every day, and LDL-cholesterol < 120 with gum bleeding (odds ratio : 0.140, 95% confidence interval : 0.036-0.540 ; OR : 0.085, 95% CI : 0.010-0.736, OR : 0.275, 95% CI : 0.077-0.979, respectively). Conclusions : Our findings suggest that toothbrushing before bedtime every night is associated with reduced risk of obesity and that eating slowly and chewing well are advantageous for glycemic control in patients with type 2 diabetes.J. Med. Invest. 68 : 140-147, February, 2021.

Long-Term Outcomes for Cementless Anatomic Femoral Components, Compared by Area of Porous Coating, in Patients Younger Than 50 Years Treated for Hip Dysplasia.

BACKGROUND: We investigated whether the proximal circumferential porous coating of cementless stems would make implant survival of >20 years possible in young patients. METHODS: Data for patients younger than 50 years with hip dysplasia who had an anatomic stem implanted with a proximal porous coating with hydroxyapatite/tricalcium phosphate were reviewed. Noncircumferential porous (non-C-type) stems were used in 17 hips (13 cases), and circumferential porous (C-type) stems were used in 87 hips (68 cases). Acetabular components with conventional polyethylene were used for all hips. The mean ages at surgery for patients with non-C-type stems and those with C-type stems were 43.3 and 44.7 years, respectively. Stems that had not loosened were retained at the time of acetabular revision. The average duration of follow-up for patients with non-C-type stems was 26.9 years and was 22.3 years for those with C-type stems. RESULTS: Mean survival rates as determined by the Kaplan-Meier method were 74.9% at 20 years and 59.9% at 25 years for non-C-type stems and were 100% at 20 years and 94.0% at 25 years for C-type stems. The survivorship for C-type stems was significantly higher than that for non-C-type stems (P < .01). Focal osteolysis in the shoulder of 37 hips with C-type stems suppressed the spread of osteolysis to the distal femur. CONCLUSION: Anatomic femoral stems with a circumferential porous coating provide excellent durability in patients with hip dysplasia who are 50 years of age or younger. LEVEL OF EVIDENCE: Therapeutic Level IV.

Involvement of oral bacteria and oral immunity as risk factors for chemotherapy-induced fever with neutropenia in patients with hematological cancer.

The aim of this study is to investigate the association between chemotherapy-induced fever with neutropenia less than 1500/µL (FwN) and oral bacteria and/or oral immunity in patients with hematological cancer. Thirty-two patients with hematological cancer were enrolled in the study. Secretory immunoglobulin A (sIgA) in saliva and the anaerobic bacteria in tongue coating of each subject were assessed before the first chemotherapy. Eleven subjects had an onset of FwN and 21 subjects did not during the observation periods. It was revealed by the Cox-proportional hazard model analysis that the levels of sIgA were low (HR 0.98, p < 0.05) and the rate of Fusobacterium nucleatum [F. nucleatum count per total bacterial count (%)] was high (HR 1.65, p < 0.05) in patients with FwN onset. Using ROC curve analysis, the optimal cutoff point based on the AUC in the F. nucleatum/sIgA ratio was 0.023, and this model had a 78.4% probability (p < 0.01). The risk of FwN onset was also significantly higher among the group of ≥ 0.023 F. nucleatum/sIgA ratio (HR 66.06, p < 0.01). These results suggest that the rate of F. nucleatum and the levels of sIgA at baseline might be related to FwN onset as risk factors.

Association between Oral Health Status and Diabetic Nephropathy-Related Indices in Japanese Middle-Aged Men.

Oral health status is known to be associated with lifestyle-related diseases such as diabetes and chronic kidney disease. In Japan, around 40% of hemodialysis cases are patients with diabetic nephropathy. The aim of this study was to clarify the association between oral health status and diabetic nephropathy-related indices in Japanese middle-aged men. Sixty-six men (age range: 55-64 years) with ≥20 remaining teeth and who received public medical checkups and oral examinations were enrolled. We examined correlations of age, body mass index, HbA1c, HDL-C, LDL-C, neutral fat, serum creatinine, and the estimated glomerular filtration rate (eGFR) with the number of remaining teeth or the community periodontal index (CPI) score (periodontal pocket < 4 mm: 0, 4-6 mm: 1, ≥6 mm: 2). A positive correlation between the CPI score and serum creatinine and a negative correlation between CPI score and eGFR (Spearman's rank correlation coefficient, r = 0.459, p < 0.01, and r = -0.460, p < 0.01, respectively) were observed. The mean eGFR in the CPI score 0 group was significantly higher than that in the CPI score 1/2 group (82.6 vs. 70.7, Student's t-test, p < 0.01). Logistic regression analysis using eGFR as a dependent variable and age, CPI score, body mass index, HbA1c, and neutral fat as independent variables suggested that low eGFR (<60) could be attributed to CPI score (OR = 3.169, 95% CI: 1.031-9.742, p = 0.044). These results suggest a possible association between periodontal status and renal function in Japanese middle-aged men. Periodontal condition is controlled by oral prophylaxis, and periodontal disease and chronic kidney disease have some common risk factors. Thus, periodontal management can contribute to the prevention of severe chronic kidney disease.

Effectiveness of an oral care tablet containing kiwifruit powder in reducing oral bacteria in tongue coating: A crossover trial.

OBJECTIVES: The aim of this study was to investigate the effect of an oral care tablet containing kiwifruit powder on oral bacteria in tongue coating compared with tongue brushing. MATERIAL AND METHODS: Thirty-two healthy, young adults were enrolled, and a crossover clinical trial was conducted. The volatile sulfur compound (VSC) concentration, Winkel tongue-coating index (WTCI), and the number of total bacteria in addition to Fusobacterium nucleatum in tongue coating were measured. We instructed subjects to remove tongue coating by tongue brush for Intervention I, to keep the oral care tablet containing kiwifruit powder on the tongue dorsum and to let it dissolve naturally for Intervention II, and three oral care tablets 1 day before the measurement for Intervention III. RESULTS: There were significant differences in terms of the level of H2 S, VSC, and WTCI at Intervention I and all evaluation values at Intervention II. There were significant differences in terms of the level of H2 S, VSC, WTCI, the number of total bacteria, and F. nucleatum at Intervention III. The value of WTCI, the number of bacteria, and F. nucleatum decreased significantly after taking the oral care tablets than after tongue brushing. When compared with Interventions I and III, Intervention III showed the effective results; there were significant differences in the number of total bacteria and F. nucleatum between tongue brushing and taking tablets. CONCLUSIONS: These results suggested that the oral care tablet containing kiwifruit powder could be effective in reducing total bacteria and F. nucleatum in tongue coating when compared with tongue brushing.

Yokukansan, a Kampo medicine, enhances the level of neuronal lineage markers in differentiated P19 embryonic carcinoma cells.

Yokukansan (YKS), a traditional Japanese Kampo medicine, affects neurological and psychiatric disorders. It ameliorates hippocampal neurogenesis in animals. However, its effect on neuronal cell differentiation remains unclear. Therefore, we investigated the effects of YKS on pluripotent P19 embryonic carcinoma cells as neuronal differentiation model cells. Western blotting and immunocytochemistry revealed that 10 µg/mL YKS treatment during embryoid body formation or neuronal differentiation increased the expression of the neuronal stem cell marker, Nestin, by 1.9-fold and 1.7-fold, respectively, and of the mature neuron marker, NeuN, by 1.5-fold and 1.4-fold, respectively. We examined the effect of YKS on intracellular signaling pathways in P19 cells and found significant elevation in phospho-PDK1 and phospho-mTOR expression (1.1-fold and 1.2-fold, respectively). Therefore, we investigated the effect of PDK1 and mTOR inhibitors on the level of neuronal lineage markers. We found that the mTOR inhibitor significantly abolished the YKS effect on the level of neuronal lineage markers. Moreover, to identify the target(s) of YKS, antibody array analysis that simultaneously detects 16 phosphorylated proteins was performed. YKS significantly upregulated 10 phosphorylated proteins including PDK1, Akt, AMPK, PRAS40, mTOR, p70 S6 kinase, GSK-3α, Bad and ERK1/2 under cell proliferation conditions. These results suggest that YKS simultaneously activates multiple signaling pathways. Thus, we concluded that YKS enhances the level of neuronal lineage markers in differentiated P19 cells, however it does not induce neuronal differentiation. Furthermore, mTOR is the predominant mediator of the YKS effect on these cells.

Visible light-induced heterogeneous Meerwein-Ponndorf-Verley-type reduction of an aldehyde group over an organically modified titanium dioxide photocatalyst.

An organically modified titanium dioxide photocatalyst prepared by a simple impregnation method chemoselectively and almost quantitatively converted benzaldehydes having other reducible functional groups to the corresponding benzyl alcohols under visible light irradiation.