Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning.

PURPOSE: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. METHODS: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. RESULTS: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (ß = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. CONCLUSION: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

The Impact of Nutrition and Oral Function Exercise on among Community-Dwelling Older People.

Oral function (OF) decline in older people is associated with nutritional deficiencies, which increases frailty risk and the need for nursing care. We investigated whether the delivery of an oral function improvement program on a tablet device was as effective as delivery through a paper-based program. We also investigated the association between tongue pressure (TP) improvement and nutritional status at the baseline. The participants involved in the study were 26 community-dwelling older people with low TP, <30 kPa, aged ≥65 years, who were enrolled in a randomized controlled trial for a month in Itoshima City, Fukuoka, Japan. Oral and physical functions and body composition were measured at the baseline and at follow-up. Two-way analysis of variance revealed that body mass index (p = 0.004) increased, and maximum masticatory performance (p = 0.010), maximum TP (p = 0.035), and oral diadochokinesis /pa/ and /ka/ (p = 0.009 and 0.017, respectively) improved in a month. Participants with higher TP improvement showed an increased intake of animal proteins at the baseline: fish (p = 0.022), meat (p = 0.029), and egg (p = 0.009). OF exercises for improving TP were associated with higher animal protein intake at the baseline. This study has been registered with the UMIN Clinical Trials Registry (UMIN 000050292).

Association between oral function and physical pre-frailty in community-dwelling older people: a cross-sectional study.

BACKGROUND: Few studies have examined the relationship between oral functions and the physical pre-frailty status, classified using physical function tests. This cross-sectional study aimed to clarify this association among community-dwelling older people from the Itoshima Frail Study in Itoshima Fukuoka Prefecture. METHODS: Of the 1,555 individuals invited to join the study, 381 (188 males and 193 females) enrolled. Their physical pre-frailty was assessed with a classification system consisting of two physical indicators (fatigue and unintentional weight loss, determined with a questionnaire), two functional components (declined walking speed and muscle weakness, determined using a body function measuring instrument), and declined physical activity (examined using a triaxial accelerometer). Subsequently, the individuals were classified into three groups: robust, pre-frailty, and frailty. Along with the number of teeth remaining, oral functions, such as masticatory performance, tongue pressure strength, and oral diadochokinesis (ODK), were examined. Data regarding social activity and exercise habits were collected, and the individuals' body compositions were measured. Odds ratios (ORs) and 95% confidence intervals (CIs) for the physical pre-frailty were calculated using logistic regression models. RESULTS: In this study, 126 (33%) participants presented with physical pre-frailty. The participants in the robust group were younger, had stronger maximum handgrip strength, and walked faster than those in the physical pre-frailty group (p < 0.001). The robust group presented with better oral functions (masticatory performance, p = 0.015; oral ODK /ta/, p = 0.004). The physical pre-frailty status was significantly associated with age (OR, 1.111; 95% CI, 1.048-1.178; p < 0.001), masticatory performance (OR, 0.819; 95% CI, 0.680-0.986; p = 0.035), low ODK/ta/ (OR, 1.864; 95% CI, 1.069-3.250; p = 0.028), and low social activity (OR, 2.273; 95% CI, 1.308-3.951; p = 0.004). CONCLUSION: This study indicated that older people with higher age, lower anterior tongue movement, lower masticatory performance, and lower social activity are positively associated with physical pre-frailty.

Primary Teeth-Derived Demineralized Dentin Matrix Autograft for Unilateral Maxillary Alveolar Cleft during Mixed Dentition.

This clinical report describes the immediate autograft of primary (milk) teeth-derived demineralized dentin matrix (DDM) granules for a 6-year-old boy with unilateral alveolar cleft. First, four primary teeth were extracted, crushed in an electric mill for 1 min, and the crushed granules were demineralized in 2% HNO3 solution for 20 min. Simultaneously, the nasal mucoperiosteum was pushed upwards above the apices of the permanent central incisor adjacent to the cleft. The nasal and palatal openings were closed by suturing the mucoperiosteum on both sides of the cleft with absorbable threads. The wet DDM granules were grafted into the managed cleft triangle space, and a labial flap was repositioned. The radiographic images at 6 months showed the continuous hard tissues in the cleft area and DDM granules onto lateral incisor (22) and impacted canine (23). The 3D-CT views at 2 years showed impacted tooth (22) blocked by primary canine and the replacement of DDM granules by bone near teeth (22,23). At 4 years, tooth crown (22) was situated just under the mucous membrane, and teeth (22,23) erupted spontaneously until 6 years without a maxillary expansion and a tow guidance of canine. The DDM granules contributed to bone formation without the inhibition of spontaneous tooth eruption. We concluded that autogenous primary teeth DDM graft should become a minimally invasive procedure without bone harvesting and morbidities for unilateral alveolar cleft.

Histological Evidences of Autograft of Dentin/Cementum Granules into Unhealed Socket at 5 Months after Tooth Extraction for Implant Placement.

The aim of this clinical case study was to observe biopsy tissues at 5 months after an autograft of a partially demineralized dentin/cementum matrix (pDDM) into a tooth-extracted socket exhibiting healing failure. A 66-year-old female presented with healing failure in the cavity for 2 months after the extraction (#36). Initial X-ray photos showed a clear remainder of lamina dura (#36), a residual root (#37), and a horizontal impaction (#38). The vital tooth (#38) was selected for pDDM. The third molar crushed by electric mill was decalcified in 1.0 L of 2.0% HNO3 for 20 min and rinsed in cold distilled water. The pDDM granules (size: 0.5-2.0 mm) were grafted immediately into the treated socket. X-ray views just after pDDM graft showed radio-opaque granules. At 5 months after pDDM graft, the surface of regenerated bone was harmonized with the mandibular line, and bone-like radio-opacity was found in the graft region. The biopsy tissue (diameter: 3.0 mm) at 5 months after pDDM graft showed that mature bone was interconnected with the remaining pDDM. The novel histological evidence highlighted that newly formed bone was connected directly with both dentin-area and cementum-area matrix of pDDM. We concluded that pDDM contributed to the regeneration of bone in the unhealed socket, and this regeneration prepared the socket for implant placement. Autogenous pDDM could be immediately recycled as an innovative biomaterial for local bone regeneration.

Effect of Isometric Tongue Lifting Exercise on Oral Function, Physical Function, and Body Composition in Community-Dwelling Older Individuals: A Pilot Study.

INTRODUCTION: It is known that oral frailty is one of the risk factors for physical frailty. Therefore, early detection, appropriate treatment, and prevention of oral frailty are really important. Tongue lifting exercise has been identified as a well-known method for improving decreased tongue pressure, one of the factors for oral frailty. However, few reports have investigated how tongue-strengthening exercises affect physical function and body composition. The aim of this study was to investigate the effects of isometric tongue lifting exercises on oral function, physical function, and body composition. METHODS: Participants were 49 elderly people aged 68-79 years, who had previously participated in the "Itoshima Frail Study." Participants performed isometric tongue lift exercises for 3 months. Oral function (tongue pressure and oral diadocokinesis), physical function (grip strength, open-eyed one-leg standing, sit-to-stand motion time, 5-m gait speed, and 3-m Timed up and go [TUG]), and body composition were measured at baseline and post-intervention, and the extent of changes in each item was statistically analyzed. Furthermore, participants were divided into physical frailty/pre-frailty and robust groups based on the Japanese version of the frail scale proposed by [BMC Geriatr. 2015 Apr;15:36] and were compared in terms of the extent of changes in each item baseline and the post-intervention. RESULTS: After the intervention, oral function increased significantly together with a significant improvement in physical function, open-eyed one-leg standing time, sit-to-stand motion, and 3-m TUG. For body composition, visceral fat level and basal metabolic rate decreased significantly. Although no significant change in body composition was observed in the physical frailty/pre-frailty group after the intervention, significant improvements in several items were observed in the robust group. CONCLUSION: Isometric tongue lifting exercise can effectively improve oral function. Furthermore, it might affect physical function and body composition.

Factors That Influence the Judgment of Oral Management Necessity in Preoperative Oral Screening.

Oral management during the perioperative period is important to prevent the development of postoperative complications. However, there are no unified systems to examine the oral status of patients and very few studies have focused on preoperative oral screening. In this study, we examined the oral status of patients who underwent oral screening at a University Hospital. A total of 1173 patients who underwent oral screening for perioperative management from April 2020 to July 2021 were enrolled. The subjects' medical data were retrospectively extracted from the dental records, and finally, the data of 1081 patients aged ≥20 years were analyzed. Oral screening based on seven categories was performed by dentists or dental hygienists. Our cumulative results determined whether patients required oral management during the perioperative period. "Poor oral hygiene" was the most frequent category (24%) of all oral categories examined. Logistic analysis revealed that tooth mobility had the highest odds ratio (21.476; 95% confidence interval: 11.462-40.239; p < 0.001) for oral management necessity during the perioperative period. Our study suggests that poor oral hygiene is most frequently observed in preoperative oral screening. Moreover, tooth mobility in preoperative oral screening may influence the judgment of oral management necessity during the perioperative period.

Porphyromonas Gingivalis Infection Induces Synaptic Failure via Increased IL-1ß Production in Leptomeningeal Cells.

BACKGROUND: Studies have reported that synaptic failure occurs before the Alzheimer's disease (AD) onset. The systemic Porphyromonas gingivalis (P. gingivalis) infection is involved in memory decline. We previously showed that leptomeningeal cells, covering the brain, activate glial cells by releasing IL-1ß in response to systemic inflammation. OBJECTIVE: In the present study, we focused on the impact of leptomeningeal cells on neurons during systemic P. gingivalis infection. METHODS: The responses of leptomeningeal cells and cortical neurons to systemic P. gingivalis infection were examined in 15-month-old mice. The mechanism of IL-1ß production by P. gingivalis infected leptomeningeal cells was examined, and primary cortical neurons were treated with P. gingivalis infected leptomeningeal cells condition medium (Pg LCM). RESULTS: Systemic P. gingivalis infection increased the expression of IL-1ß in leptomeninges and reduced the synaptophysin (SYP) expression in leptomeninges proximity cortex in mice. Leptomeningeal cells phagocytosed P. gingivalis resulting in lysosomal rupture and cathepsin B (CatB) leakage. Leaked CatB mediated NLRP3 inflammasome activation inducing IL-1ß secretion in leptomeningeal cells. Pg LCM decreased the expression of synaptic molecules, including SYP, which was inhibited by an IL-1 receptor antagonist pre-treatment. CONCLUSION: These observations demonstrate that P. gingivalis infection is involved in synaptic failure by inducing CatB/NLRP3 inflammasome-mediated IL-1ß production in leptomeningeal cells. The periodontal bacteria-induced synaptic damage may accelerate the onset and cognitive decline of AD.

GSK3ß is involved in promoting Alzheimer's disease pathologies following chronic systemic exposure to Porphyromonas gingivalis lipopolysaccharide in amyloid precursor proteinNL-F/NL-F knock-in mice.

In line with the strong association between periodontitis and Alzheimer's disease (AD) clinically, preclinical studies have shown that systemic exposure to Porphyromonas gingivalis (Pg) initiates AD pathologies. However, the involvement of periodontitis in promoting AD pathologies is unclear. In the present study, we provided evidence that chronic systemic exposure to lipopolysaccharide derived from Pg (PgLPS, 1 mg/kg, daily, intraperitoneally) prompted neuroinflammation and tau hyperphosphorylation in 10-month-old of amyloid precursor protein (APP) knock-in mice, a model of AD, carrying the Swedish and Beyreuther/Iberian mutation (APPNL-F/NL-F). The learning and memory function were assessed using the passive avoidance test. The production of APP, Amyloid (A)ß1-42, cytokines, synaptic proteins and the activation of glycogen synthase kinase (GSK)-3ß as well as phosphorylation of tau were analyzed by immunohistochemistry, Western blotting or an enzyme-linked immunosorbent assay (ELISA) in the cortex of APPNL-F/NL-F mice. We found that systemic exposure of PgLPS for three consecutive weeks induced learning and memory deficits with significantly reduced postsynaptic density protein (PSD95). Increased hyperphosphorylation of tau in multiple residues, including Ser202, Thr231 and Ser396, but not the accumulation of Aß1-42 was detected in the neurons of APPNL-F/NL-F mice. Furthermore, PgLPS increased the GSK3ß activity by reducing its phosphorylation of the serine residue at position 9 (Ser9) and promoted neuroinflammation by increasing the expression of interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF-α) while decreasing that of interleukin-10 (IL-10) and transforming growth factor (TGFß) in the cortex of APPNL-F/NL-F mice. Moreover, the PgLPS-increased GSK3ß activity was detected in both microglia and neurons, while the PgLPS-increased TNF-α expression was mainly detected in the microglia in the cortex of APPNL-F/NL-F mice. In in vitro studies, PgLPS (1 µg/ml) stimulation increased the mRNA and protein level of TNF-α in MG6 microglia, which were significantly inhibited by the GSK3ß-specific inhibitor TWS119. In contrast, the tau hyperphosphorylation and activation of GSK3ß in N2a neurons were enhanced after treatment with conditioned medium from PgLPS-stimulated microglia, which was attenuated after pre-treatment with TNF-α inhibitor. Taken together, these findings indicate that GSK3ß is involved in prompting microglia (TNF-α)-dependent tau hyperphosphorylation in neurons, resulting in learning and memory deficits in APPNL-F/NL-F mice without changes in the Aß expression during chronic systemic exposure to PgLPS. We propose that dampening GSK3ß activation may help delay the periodontitis-promoted pathological progression of AD.

Receptor for advanced glycation end products up-regulation in cerebral endothelial cells mediates cerebrovascular-related amyloid ß accumulation after Porphyromonas gingivalis infection.

Cerebrovascular-related amyloidogenesis is found in over 80% of Alzheimer's disease (AD) cases, and amyloid ß (Aß) generation is increased in the peripheral macrophages during infection of Porphyromonas gingivalis (P. gingivalis), a causal bacterium for periodontitis. In this study, we focused on receptor for advanced glycation end products (RAGE), the key molecule involves in Aß influx after P. gingivalis infection to test our hypothesis that Aß transportation from periphery into the brain, known as "Aß influx," is enhanced by P. gingivalis infection. Using cultured hCMEC/D3 cell line, in comparison to uninfected cells, directly infection with P. gingivalis (multiplicity of infection, MOI = 5) significantly increased a time-dependent RAGE expression resulting in a dramatic increase in Aß influx in the hCMEC/D3 cells; the P. gingivalis-up-regulated RAGE expression was significantly decreased by NF-κB and Cathepsin B (CatB)-specific inhibitors, and the P.gingivalis-increased IκBα degradation was significantly decreased by CatB-specific inhibitor. Furthermore, the P. gingivalis-increased Aß influx was significantly reduced by RAGE-specific inhibitor. Using 15-month-old mice (C57BL/6JJmsSlc, female), in comparison to non-infection mice, systemic P. gingivalis infection for three consecutive weeks (1 × 108  CFU/mouse, every 3 days, intraperitoneally) significantly increased the RAGE expression in the CD31-positive endothelial cells and the Aß loads around the CD31-positive cells in the mice's brains. The RAGE expression in the CD31-positive cells was positively correlated with the Aß loads. These observations demonstrate that the up-regulated RAGE expression in cerebral endothelial cells mediates the Aß influx after P. gingivalis infection, and CatB plays a critical role in regulating the NF-κB/RAGE expression. Cover Image for this issue: https://doi.org/10.1111/jnc.15073.

The Association of Oral Function with Oral Health-Related Quality of Life in University Students: A Cross-Sectional Pilot Study.

The aim of this cross-sectional study was to investigate the association between oral function and oral health-related quality of life (OHRQoL) in healthy university students. Oral functions and OHRQoL (General Oral Health Assessment Index; GOHAI) were investigated in 58 healthy university students. Oral functions, such as tongue pressure, tongue-lip motor function, occlusal force, and masticatory function, were examined. The participants were divided into two groups based on low and high GOHAI scores. Information about oral health, dental caries treatment history, insomnia, and personality and lifestyle was obtained using a self-reported questionnaire. Oral mucosal wetness scores and tongue-lip motor functions (oral diadochokinesis /ka/) were significantly decreased in the low GOHAI score group compared to the high GOHAI score group (p = 0.001 and p = 0.017, respectively). In the logistic regression model, the GOHAI score was independently associated with the oral mucosal wetness score (odds ratio (OR) = 0.622; 95% confidence interval (CI), 0.411-0.941; p = 0.025) and oral diadochokinesis /ka/ (OR = 0.376; 95% CI, 0.170-0.832; p = 0.016). Our study demonstrated the presence of low oral function in university students and suggested its association to low OHRQoL in this population.

Opportune Time of Tooth Extraction in Individuals Requiring Ventricular Assist Device Implantation: A Retrospective Cohort Study.

PURPOSE: Individuals with implantable ventricular assist devices (VADs) are at extremely high risk of bleeding, thromboembolism, and infection after undergoing invasive dental procedures. This study aimed to investigate the systemic and local complications of tooth extraction before and after VAD implantation. PATIENTS AND METHODS: This retrospective cohort study was conducted at a single center. Oral surgical procedures were performed in patients before and/or after left VAD implantation for bridge-to-heart transplantation between April 2013 and December 2017. In this study, the medical charts of the patients were retrospectively reviewed. Data about pre-extraction complete blood count, coagulation profile, biochemical profile, and incidence of local and systemic complications were compared in patients undergoing tooth extraction before VAD implantation (b-VAD group) versus after VAD implantation (a-VAD group). RESULTS: In total, 28 inpatients underwent 36 oral surgical procedures before and/or after VAD implantation. Moreover, 24 tooth extractions were performed in the b-VAD group, and 12 were performed in the a-VAD group. The incidence of post-extraction bleeding was higher in the a-VAD group (P = .001, Mann-Whitney U test), and a significant difference was observed in terms of activated partial thromboplastin time (P = .010, Mann-Whitney U test). Systemic complications associated with VADs included cerebral infarction (n = 2) and driveline infection (n = 1). Post-extraction bleeding was observed within 90 days after VAD implantation in all patients who underwent tooth extraction. CONCLUSIONS: The risk of bleeding after tooth extraction was higher in the a-VAD group (67%) than in the b-VAD group (13%). In 3 cases, VAD-related systemic complications developed within a short period after tooth extraction. The extraction management in the b-VAD group could be controlled without causing any problem. Hence, the opportune time of tooth extraction is before VAD implantation.

Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation.

Disruption of the intestinal microbiota caused by intensive chemotherapy, irradiation and antibiotics can result in development of severe gut graft-versus-host disease and infectious complications, leading to poorer outcomes among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the oral cavity is also densely colonized by indigenous microorganisms, the bacterial composition in allo-HSCT recipients remains unclear. We determined the tongue microbiota composition of 45 patients with hematological disorders on the day of transplantation and compared them to 164 community-dwelling adults. The V1-V2 regions of the 16S rRNA gene sequences demonstrated that the allo-HSCT recipients had less diverse and distinct microbiota from that of community-dwelling adults. The full-length 16S rRNA gene sequences identified 146 bacterial taxa in the microbiota of allo-HSCT recipients, of which 34 bacterial taxa did not correspond to bacteria primarily inhabiting the oral cavity deposited in the expanded Human Oral Microbiome Database. Notably, the detection of Staphylococcus haemolyticus and/or Ralstonia pickettii was significantly associated with a higher risk of mortality during the follow-up period. These results demonstrate that the oral cavity of allo-HSCT recipients is colonized by a disrupted microbiota on the day of transplantation and suggest that detection of specific nonindigenous taxa could be a predictor of transplant outcome.

A Cross-Sectional Study of Age-Related Changes in Oral Function in Healthy Japanese Individuals.

BACKGROUND: Oral function deterioration is related to a variety of factors, including aging, decline in activities of daily living, malnutrition, and cognitive decline. This cross-sectional study examined the effects of aging on oral function in healthy individuals. METHODS: A retrospective study was conducted on 175 healthy, independent patients aged 40-89 years, without dementia and with ≥20 teeth, who visited a local dental clinic in Japan. Patients were compared with 92 university students aged 20-29 years. The seven criteria proposed by the Japanese Society of Gerodontology to diagnose "oral hypofunction" were observed and statistically analyzed. RESULTS: Compared with those in the control group, the degree of tongue coating was increased in the group aged over 80 years, occlusal force was decreased in the group aged 70-79 years, tongue motor function was decreased in the groups aged 60-69 years and older, and tongue pressure was decreased in the groups aged 70-79 years and older. CONCLUSIONS: Healthy, independent individuals maintained several oral function criteria across aging, including oral mucosal wetness, occlusal force, lip motor function, masticatory function, and swallowing function. Tongue motor function and tongue pressure decreased with aging, indicating that these may be rehabilitation targets.

Porphyromonas gingivalis Infection Induces Amyloid-ß Accumulation in Monocytes/Macrophages.

Abnormal accumulation of amyloid-ß (Aß) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aß in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aß is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aß metabolism is unknown. We hypothesized that chronic P. gingivalis infection expands Aß pools in peripheral inflammatory tissues and thereby contributes to the accumulation of Aß in the brain of patients with periodontitis. We showed that the increased expression of IL-1ß, AßPP770, CatB, Aß1-42, and Aß3-42 was mainly co-localized with macrophages in the liver of P. gingivalis infected mice. Blocking CatB and NF-κB significantly inhibited the P. gingivalis-induced expression of IL-1ß, AßPP770, Aß1-42, and Aß3-42 in RAW264.7 cells. Aß3-42, but not Aß1-42, induced the significant death of macrophages, and the reduction of phagocytic abilities induced by Aß3-42 tended to be higher than that induced by Aß1-42. Additionally, the expression of AßPP770, CatB, Aß1-42, and Aß3-42 was determined in the macrophages of gingival tissues from periodontitis patients. These findings indicate that chronic systemic P. gingivalis infection induces the Aß accumulation in inflammatory monocytes/macrophages via the activation of CatB/NF-κB signaling, thus suggesting monocytes/macrophages serve as a circulating pool of Aß in patients with periodontitis. Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression.

Dominant-negative p53 mutant R248Q increases the motile and invasive activities of oral squamous cell carcinoma cells.

The tumor suppressor gene TP53 (gene) codes for a transcription factor which transactivates its target genes responsible for cell cycle arrest, DNA repair, apoptosis, and senescence. TP53 is well known to be the most frequent target of genetic mutations in nearly half of human cancers including oral squamous cell carcinoma (OSCC). Many p53 mutants including R248Q and R248W not only lose its tumor-suppressor activities, but also interfere with the functions of wild-type p53; this is so-called dominant-negative (DN) mutation. The DN p53 mutation is a predictor of poor outcome in patients with various cancers, and also a risk factor for metastatic recurrence in patients with OSCC. Recently it has been reported that DN p53 mutants acquire new oncogenic activities, which is named gain-of-function (GOF). This study aimed at determining whether R248Q and R248W were involved in OSCC cells' acquiring aggressive phenotypes, using SAS, HSC4 and Ca9-22 cell lines. First, two mutants p53, R248Q and R248W, were respectively transfected into SAS cells harboring recessive-type p53 (E336X). As a result, SAS cells expressing R248Q showed highly spreading, motile and invasive activities compared to parent or mock-transfected cells whereas those expressing R248W did not increase those activities. Secondly, in HSC4 cells harboring R248Q and Ca9-22 cells harboring R248W, expressions of the mutants p53 were inhibited by the transfection with siRNAs targeting p53. The inhibition of the mutants p53 decreased spreading, motile and invasive activities of HSC4 cells whereas it did not affect those activities of Ca9-22 cells. These findings suggest that R248Q p53 mutation, but not R248W p53 mutation, induces more motile and invasive potentials in human OSCC cells.

Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD.

Allogeneic hematopoietic stem cell transplantation is a curable treatment for hematological diseases. Graft-versus-host disease (GVHD) causes morbidity and mortality after HSCT. Methotrexate (MTX) is used for GVHD prophylaxis, but its appropriate dose remains unclear. In the present study, we compared the efficacy and toxicity of 15-10-10 MTX (day +1: 15 mg/m(2); days +3 and +6: 10 mg/m(2)) with 10-7-7 MTX (day +1: 10 mg/m(2); day +3 and +6: 7 mg/m(2)) in combination with tacrolimus. The cumulative incidence rates of grades II-IV acute GVHD, grades III-IV acute GVHD and chronic GVHD in the 15-10-10 MTX and 10-7-7 MTX groups did not differ to a statistically significant extent. The median time for neutrophil engraftment in the 15-10-10 MTX group was 16 days (range, 11-31 days), while that in the 10-7-7 group was 15 days (range, 12-19 days) (P = 0.024). Moreover, the median time for platelet recovery was significantly shorter in the 10-7-7 MTX group (22 days; range, 13-49 days) than that in the 15-10-10 MTX group (27 days; range, 9-405 days) (P = 0.027). The duration of oral mucositis was significantly shorter in the patients who received a reduced dose of MTX (median, 4.5 vs 13.0 days; P = 0.013). In conclusion, GVHD prophylaxis with a reduced dose of MTX was associated with earlier engraftment and earlier recovery from mucositis in comparison to a standard dose of MTX, without affecting the incidence of GVHD.

Relationship between acetaldehyde concentration in mouth air and tongue coating volume.

OBJECTIVE: Acetaldehyde is the first metabolite of ethanol and is produced in the epithelium by mucosal ALDH, while higher levels are derived from microbial oxidation of ethanol by oral microflora such as Candida species. However, it is uncertain whether acetaldehyde concentration in human breath is related to oral condition or local production of acetaldehyde by oral microflora. The aim of this pilot study was to investigate the relationship between physiological acetaldehyde concentration and oral condition in healthy volunteers. MATERIAL AND METHODS: Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years old) participated in the present study. Acetaldehyde concentration in mouth air was measured using a portable monitor. Oral examination, detection of oral Candida species and assessment of alcohol sensitivity were performed. RESULTS: Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5, 306.3) ppb. Acetaldehyde concentration in participants with a tongue coating status score of 3 was significantly higher than in those with a score of 1 (p<0.017). After removing tongue coating, acetaldehyde concentration decreased significantly (p<0.05). Acetaldehyde concentration was not correlated with other clinical parameters, presence of Candida species, smoking status or alcohol sensitivity. CONCLUSION: Physiological acetaldehyde concentration in mouth air was associated with tongue coating volume.

Relationship between acetaldehyde concentration in mouth air and tongue coating volume

Objective Acetaldehyde is the first metabolite of ethanol and is produced in the epithelium by mucosal ALDH, while higher levels are derived from microbial oxidation of ethanol by oral microflora such as Candida species. However, it is uncertain whether acetaldehyde concentration in human breath is related to oral condition or local production of acetaldehyde by oral microflora. The aim of this pilot study was to investigate the relationship between physiological acetaldehyde concentration and oral condition in healthy volunteers. Material and Methods Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years old) participated in the present study. Acetaldehyde concentration in mouth air was measured using a portable monitor. Oral examination, detection of oral Candida species and assessment of alcohol sensitivity were performed. Results Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5, 306.3) ppb. Acetaldehyde concentration in participants with a tongue coating status score of 3 was significantly higher than in those with a score of 1 (p<0.017). After removing tongue coating, acetaldehyde concentration decreased significantly (p<0.05). Acetaldehyde concentration was not correlated with other clinical parameters, presence of Candida species, smoking status or alcohol sensitivity. Conclusion Physiological acetaldehyde concentration in mouth air was associated with tongue coating volume. .

Factors associated with dry mouth in dependent Japanese elderly.

OBJECTIVES: To identify factors associated with dry mouth. BACKGROUND: Dry mouth adversely affects oropharyngeal health, particularly in elderly, and can lead to pneumonia. A better understanding of the epidemiology of dry mouth is therefore important in improving treatment strategies and oral health in high-risk elderly patients. METHODS: We conducted a cross-sectional study involving 383 dependent Japanese elderly individuals (65-84 [n = 167] and ≥85 [n = 216] years) at eight long-term care facilities and hospitals. Thirty-four potential factors associated with dry mouth were examined by multiple logistic regression analysis. The primary outcome was dry mouth, as diagnosed by tongue dorsum moisture. RESULTS: We identified that body mass index and severity of physical disability were identified as a potential factors associated with dry mouth in the super-elderly (≥85 years) group, whereas severity of physical disability, outcome measurement time, high daily water consumption, mouth breathing, use of antidepressants and diuretics, and high frequency of daily brushing (≥2 times per day; Odds ratio: 5.56; 95% Confidence Interval: 1.52-20.00) were associated with dry mouth in the 65- to 84-year-old group. CONCLUSION: To our knowledge, this is the first study to identify a link between frequency of daily brushing and dry mouth and suggests that tooth brushing should be encouraged in high-risk dependent Japanese elderly (65-84 years), particularly those taking antidepressants and/or diuretics.