BAP1 depletion in human B-lymphoblast cells affects the production of innate immune cytokines and chemokines.

BRCA1 associated protein 1 (BAP1) is a ubiquitin C-terminal hydrolase that deubiquitinates histone H2AK119ub and other proteins and regulates the expression of multiple genes. The knockout of this tumor suppressor gene results in severe thymic atrophy, complete loss of the T cell lineage, and abnormal B cell development in mice. In the current study, we investigated in vitro effects of BAP1 knockout on cytokine and chemokine production using the human B-lymphoblast cell line TSCE5. We confirmed that knockout changed the production of innate immune-associated genes and their receptors. The CCL19, CCR7, CCL2, and CXCR5 genes associated with T and B cell migration were upregulated. Knockout cells producing high levels of CCL19 showed acceleration of actin polymerization, which is essential for cell migration. CD69, PTPRC, and TLR3 genes that activate inflammation were downregulated. The tumor necrosis factor ligand genes TNF, LTA, and TNFSF10 were downregulated by knockout. In knockout cells, TNFα production was strongly downregulated upon the addition of H2 O2 , but NF-κB in the basal condition and when TNFα was added was augmented, suggesting that these cells could respond to TNFα. These results indicated that BAP1 affects the expression of chemokines and cytokines, T and B cell migration, and activated inflammation associating with innate immunity.

Adenosine Deaminase in Pleural Effusion and Its Relationship with Clinical Parameters in Patients with Malignant Pleural Mesothelioma.

Pleural effusion adenosine deaminase (ADA) levels are elevated in various diseases. We investigated whether pleural effusion ADA levels differ among patients with malignant pleural mesothelioma (MPM), lung cancer (LC), and benign diseases, including tuberculous pleurisy. We examined 329 patients from February 2002 to July 2013. There were 131 MPM cases with ADA levels of 32.29 IU/L; 117 LC cases with ADA levels of 21.12 IU/L; 54 benign disease cases with ADA levels of 20.98 IU/L. A significant difference existed in pleural effusion ADA levels between MPM and benign disease patients. Pleural effusion ADA levels were significantly higher in MPM patients.

Association of mastication and factors affecting masticatory function with obesity in adults: a systematic review.

BACKGROUND: A substantial number of adults suffer from obesity, that is caused by the risk factor, masticatory dysfunction. The association between mastication and obesity, however, is inconclusive. This systematic review aims to provide literature regarding the association between mastication and factors affecting masticatory function, and obesity in adults. METHODS: Four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were used to search for publications that met the following criteria: published between 2007 and 2016, written in English, and assessed the associations between mastication and obesity among the population aged ≥18 years. The included publications were analyzed based on the study design, main conclusions, and strength of evidence identified by the two authors who screened all the abstracts and full-text articles and, abstracted data, and performed quality assessments by using a critical appraisal tool, the Critical Appraisal Skills Programme Cohort Studies Checklists. RESULTS: A total of 18 articles (16 cross-sectional, 1 cohort studies, and 1 randomized controlled trial [RCT]) met our inclusion criteria and were evaluated. Poorer mastication was associated with obesity in 12 out of 16 cross-sectional studies. One cohort study showed that the obesity group displayed higher tooth loss than the normal weight group. One RCT demonstrated that gum-chewing intervention for 8 weeks significantly decreased waist circumference. CONCLUSIONS: Most studies revealed a positive association between mastication and obesity among adults. Nonetheless, most of them are cross-sectional studies, which are insufficient to demonstrate a causal relation. Further advancement requires RCT, especially an intervention of improvement of mastication and obesity needed to confirm this association.

Combination therapy with anti-programmed cell death 1 antibody plus angiokinase inhibitor exerts synergistic antitumor effect against malignant mesothelioma via tumor microenvironment modulation.

Malignant pleural mesothelioma (MPM) is an asbestos-related fatal malignant neoplasm. Although there has been no reliable chemotherapeutic regimen other than combination therapy of cisplatin and pemetrexed for two decades, combination of ipilimumab plus nivolumab brought about a better outcome in patients with MPM. Thus, cancer immunotherapy using immune checkpoint inhibitor (ICI) is expected to play a central role in the treatment of MPM. To maximize the antitumor effect of ICI, we evaluated whether nintedanib, an antiangiogenic agent, could augment the antitumor effect of anti-programmed cell death 1 (PD-1) antibody (Ab). Although nintedanib could not inhibit the proliferation of mesothelioma cells in vitro, it significantly suppressed the growth of mesothelioma allografts in mice. Moreover, combination therapy with anti-PD-1 Ab plus nintedanib reduced tumor burden more dramatically compared with nintedanib monotherapy via inducing remarkable necrosis in MPM allografts. Nintedanib did not promote the infiltration of CD8+ T cells within the tumor when used alone or in combination with anti-PD-1 Ab but it independently decreased the infiltration of tumor-associated macrophages (TAMs). Moreover, immunohistochemical analysis and ex vivo study using bone marrow-derived macrophages (BMDMs) showed that nintedanib could polarize TAMs from M2 to M1 phenotype. These results indicated that nintedanib had a potential to suppress protumor activity of TAMs both numerically and functionally. On the other hand, ex vivo study revealed that nintedanib upregulated the expression of PD-1 and PD-ligand 1 (PD-L1) in BMDMs and mesothelioma cells, respectively, and exhibited the impairment of phagocytic activity of BMDMs against mesothelioma cells. Co-administration of anti-PD-1 Ab may reactivate phagocytic activity of BMDMs by disrupting nintedanib-induced immunosuppressive signal via binding between PD-1 on BMDMs and PD-L1 on mesothelioma cells. Collectively, combination therapy of anti-PD-1 Ab plus nintedanib enhances the antitumor activity compared with respective monotherapy and can become a novel therapeutic option for patients with MPM.

The relationship between tooth loss and hypertension: a systematic review and meta-analysis.

As tooth loss is the high end of periodontal problems and edentulous individuals are at higher risk of nutritional problems like obesity, understanding the association between tooth loss and hypertension is important for improving cardiovascular health. We searched for publications from the last two decades using three electronic databases (PubMed, Web of Science and Scopus) and conducted a systematic review and meta-analysis on the association between tooth loss and hypertension according to PRISMA-P guidelines. Quality assessments were performed using the Newcastle-Ottawa Scale and the GRADE approach. Twenty-four studies (20 cross-sectional, and 4 cohort) met the inclusion criteria for this review. Most cross-sectional studies showed that subjects with more tooth loss exhibited a greater proportion of hypertension and higher systolic blood pressure than those with less tooth loss. Meta-analyses revealed a statistically significant association between tooth loss and hypertension. The pooled odds ratios of hypertension for having tooth loss with no tooth loss and for edentulous with dentate were 2.22 (95% CI 2.00-2.45) and 4.94 (95% CI 4.04-6.05), respectively. In cohort studies, subjects with more tooth loss had a greater incidence of hypertension than those with less tooth loss during the follow-up period. The present systematic review and meta-analysis suggests that tooth loss is associated with an increased risk of hypertension and higher systolic blood pressure.

The Impact of Oral Health on Respiratory Viral Infection.

Influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV-2) have caused respiratory diseases worldwide. Coronavirus disease 2019 (COVID-19) is now a global health concern requiring emergent measures. These viruses enter the human body through the oral cavity and infect respiratory cells. Since the oral cavity has a complex microbiota, influence of oral bacteria on respiratory virus infection is considered. Saliva has immune molecules which work as the front line in the biophylactic mechanism and has considerable influence on the incidence and progression of respiratory viral infection. Salivary scavenger molecules, such as gp340 and sialic acid, have been reported to exert anti-influenza virus activity. Salivary secretory immunoglobulin A (SIgA) has potential to acquire immunity against these viruses. Biological features of the oral cavity are thought to affect viral infection in respiratory organs in various ways. In this review, we reviewed the literature addressing the impact of oral conditions on respiratory infectious diseases caused by viruses.

A quick statistically accurate diagnosis for caries risk in the elderly.

BACKGROUND: In the elderly, the necessity to promote oral health is increasing to improve their quality of life. The prediction of dental caries risk makes it possible to prolong the life span of teeth. To develop a quick diagnosis system for caries risk, two methods, the modified Saliva Check SM and Saliva Check sIgA, were investigated in elderly patients. METHODS: We developed a caries risk quick assessment system using Saliva Check sIgA that specifically recognizes secretory IgA (sIgA) in saliva against the binding site of the mutans streptococci (MS) to the salivary-coated tooth surface; and combined it with a modified Saliva Check SM to determine the number of MS. One hundred eighty three patients (80 females, 103 males) who participated in 2005 (average age 77 years) and in 2006 (average age 78 years) were assessed for caries risk using the systems in this cohort study. RESULTS: Subjects with a positive Saliva Check sIgA showed a significantly lower increment of decayed and filled teeth number (DFT) on the coronal surface; whereas those testing negative had root decay and increased filled teeth numbers (RDFT) at the root surface during the following year. The combination of Saliva Check sIgA and modified Saliva Check SM showed the subjects with Saliva Check sIgA positive and modified Saliva Check SM negative had less than half of the increment of DFT than other groups. In the other groups, Saliva Check sIgA negative and modified Saliva Check SM positive detected >90% of the subjects with an MS level of >5 x 10(5)/mL of saliva in patients that were assessed in 2006. This suggests these subjects may need extensive care. CONCLUSIONS: This new combination system significantly evaluates the caries risk to predict future incidence for dental caries on the coronal surface and may be useful for risk diagnosis of caries during a visit to the dental office.

The Relationship between Vitamin C and Periodontal Diseases: A Systematic Review.

Vitamin C is important for preventing and slowing the progression of many diseases. There is significant evidence linking periodontal disease and vitamin C. We aimed to systematically review the studies addressing the relationship between vitamin C and periodontal disease, and the preventive ability of vitamin C against periodontal disease. Electric searches were performed using PubMed, EMBASE, Cochrane Library, and Web of Science. Studies addressing the relationships between periodontal disease and vitamin C in adults aged over 18 years were included. Quality assessment was done using the Critical Appraisal Skills Program guideline and GRADE-CERQual. There were 716 articles that were retrieved and 14 articles (seven cross-sectional studies, two case-control studies, two cohort studies, and three randomized controlled trials (RCT)) were selected after reviewing all of the articles. The vitamin C intake and blood levels were negatively related to periodontal disease in all seven cross-sectional studies. The subjects who suffer from periodontitis presented a lower vitamin C intake and lower blood-vitamin C levels than the subjects without periodontal disease in the two case-control studies. The patients with a lower dietary intake or lower blood level of vitamin C showed a greater progression of periodontal disease than the controls. The intervention using vitamin C administration improved gingival bleeding in gingivitis, but not in periodontitis. Alveolar bone absorption was also not improved. The present systematic review suggested that vitamin C contributes to a reduced risk of periodontal disease.

Impact of routine oral care on opportunistic pathogens in the institutionalized elderly.

Routine oral hygiene is important for the control of opportunistic pathogens in the oral cavity of institutionalized elderly individuals. We evaluated the effects of routine oral care on opportunistic pathogens at various time points after admission to a nursing home. Twenty-five elderly subjects living in the nursing home (mean age: 86.0 +/- 10.4 years) participated in the study. Caregivers and dental hygienists cleaned the teeth, dentures, tongue, and mucosa after each meal using both routine and professional oral care techniques. Opportunistic pathogens were collected from the teeth, tongue, and mucosal surfaces using a cotton swab; and the species of microbes were determined and the numbers were counted following cultivation on selective agar. Regular oral care including professional oral care was found to be effective for reducing infections by many kinds of opportunistic pathogens on the teeth surfaces and the oral environment without food residue during a long-term study (6 months). Further, this care after 1 month significantly reduced infections by opportunistic pathogens on mucosal surfaces in subjects without dentures; however, this was not observed in those with dentures. Our data shows the importance of regular oral care in cleaning hard and soft surfaces of the oral cavity improves the oral health of the institutionalized elderly.

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer].

We performed combination therapy with irinotecan (CPT-11) plus nedaplatin (254-S) for patients with cervical cancer. A total of 9 patients with cervical cancer (5 patients treated in neoadjuvant setting and 4 patients for recurrent disease) were administered 80 mg/m(2) of 254-Sintravenously on day 1 and 50 mg/m(2) of CPT-11 intravenously on day 1, 8 and 15. Treatment was repeated every 4 weeks. The average number of courses administered was 3.8 (range, 2-6). Grade 3 or 4 adverse events were leukopenia in 4 patients, thrombocytopenia in 1 patient and vomiting in 1 patient. The response rate was 40% in the neoadjuvant setting (2 PRs) and 75% in recurrent disease (3 PRs).

Psychological effects of exercise on community-dwelling older adults.

BACKGROUND: In recent years, there have been an increasing number of older adults who suffer from mental disorders globally. OBJECTIVE: The objective of this study was to examine the effect of an intervention that consisted of an exercise program to improve the mental health of community-dwelling older adults. PARTICIPANTS AND METHODS: The recruited participants of this study were community-dwelling older adults aged ≥60 years who participated in a comprehensive health promotion program in Kakogawa, Japan. Participants in the intervention group received an exercise program that was developed for older adults using Thera-Band. To measure participants' mental health status, a Japanese version of the short form of the Profile of Mood States (POMS-SF) was used. Stress markers were measured, such as salivary cortisol, alpha-amylase, and sIgA levels. All participants provided salivary samples and completed psychological questionnaires at baseline and 6-month follow-up. RESULTS: No significant differences were observed between the intervention and control groups with respect to POMS-SF score and salivary biomarker profile at baseline. After the intervention, the intervention group showed a significant decrease in the POMS-SF "fatigue" score and cortisol level. No significant changes were observed in the control group. CONCLUSION: Simultaneous changes in feelings of fatigue and cortisol levels were observed among subjects who had received the intervention of regular exercise. Further research is needed to investigate the effectiveness of exercise intervention in improving mental health among older adults.

Successful Treatment of Pulmonary Pleomorphic Carcinoma with Nivolumab: A Case Report.

Pulmonary pleomorphic carcinoma (PPC) has a poor prognosis due to the poor results of treatment with systemic chemotherapy. We report the case of a 73-year-old woman with PPC who showed a favorable response to nivolumab. As first-line treatment for postoperative recurrence, she received carboplatin and nanoparticle albumin-bound paclitaxel. However, 12 months later, a new metastatic lymph node appeared. Nivolumab was administered as second-line treatment, and the patient showed a favorable prolonged response. The effects of treatment of PPC with nivolumab seem promising. The results of a future prospective study are expected to identify indicators for the treatment of PPC.

Relationships of anti-PAc (361-386) peptide salivary IgA antibody, eosinophils and basophils with periodontal status in the elderly.

The amino acid residues 361-386 of Streptococcus mutans PAc includes an important region associated with the interaction between S. mutans and salivary components. We investigated the relationships between levels of the anti-PAc (361-386) peptide antibody (PPA) in saliva and periodontal status in 281 elderly subjects (mean age 77 years; 118 females, 163 males) by assessing dental calculus (CA), attachment loss (AL), pocket depth (PD), bleeding on probing (BOP) and various blood parameters. Enzyme-linked immunosorbent assay results revealed that subjects with a PPA level of greater than 0.1 (PPA detected group) showed a lower average value for number of sites with more than 6 mm of AL/6 points x 100/tooth (rAL6) than those with a PPA level of less than 0.1 (PPA not detected group). Furthermore, average values for rAL6 were significantly lower in the PPA detected group, and BOP, AL and rAL6 correlated positively and significantly with the percentage of eosinophils present in leukocytes in female subjects in both groups. PPA level had a negative correlation with percentages of basophils and eosinophils. The results indicate that systemic increases in numbers of eosinophils and basophils are associated with the development of periodontal diseases, while PPA level may be a useful indicator of periodontal status.

Role of salivary tumour necrosis factor alpha in HIV-positive patients with oral manifestations.

In HIV-1-infected patients, oral manifestations such as recurrent apthous ulcers are often seen. A total of 29 HIV-infected patients were examined to determine salivary tumour necrosis factor alpha (TNFalpha) concentrations by enzyme-linked immunosorbent assay, the amount of HIV-1 RNA copy by Amplicor HIV-1 Monitor test, number of CD4 cells by flow cytometry and oral manifestations by oral examination. TNFalpha concentration was significantly correlated with the amount of HIV-1 RNA, however, not with the number of CD4 cells in HIV-1-infected patients. Further, patients with oral manifestations showed significantly higher concentrations of TNFalpha in saliva and HIV-1 RNA copies in serum than those without oral manifestations. Following recovery from oral ulcers, TNFalpha concentration was decreased by half to 20 times lower than the level of that during ulcer incidence. Our results suggest that salivary TNFalpha is a good indicator for oral manifestations and HIV RNA amounts in HIV-1-infected patients.

The Associations among Psychological Distress, Coping Style, and Health Habits in Japanese Nursing Students: A Cross-Sectional Study.

Background: Nursing students in many countries have been reported to experience high levels of stress and psychological distress. Health habits could potentially mediate the association between coping styles and psychological status. The purpose of this study was to evaluate the mediation effect of health habits in the relationship between stress coping styles and psychological distress in Japanese nursing students. Methods: A total of 181 nursing students completed anonymous self-reported questionnaires comprised of the General Health Questionnaire-12 (GHQ-12), the Brief Coping Orientation questionnaire, and an additional questionnaire on health behavior. A mediation analysis using path analysis with bootstrapping was used for data analysis. Results: Multivariate linear regression analysis showed that psychological distress was significantly and positively associated with "Avoidance coping" (ß = 0.39, p < 0.001), and was negatively associated with "Active coping" (ß = -0.30, p < 0.001), "exercise habit" (ß = -0.25, p = 0.001), and "sleeping" (ß = -0.24, p = 0.002). In the path model, "Active coping" and "Avoidance coping" had significant or marginally significant associations with "exercise habits" (active: ß = 0.19, p = 0.008, avoidance: ß = -0.12, p = 0.088), and psychological distress (active: ß = -0.25, p < 0.001, avoidance: ß = 0.363, p < 0.001). However, these coping style variables did not have a significant association with "sleep". In general, the size of the correlations was below 0.4. Conclusions: Exercise habits mediated the relationship between coping styles and psychological distress to a greater extent than sleep. The present study suggests the possibility that complex interactions between health habits and coping styles may influence the psychological status of nursing students.

Association between mastication and cognitive status: A systematic review.

PURPOSE: A substantial number of elderly people suffer from cognitive impairment and dementia, which are considered to have various risk factors, including masticatory dysfunction; however, the association between mastication and cognition is inconclusive. The objectives of this systematic review were to provide an overview of the literature on (1) the association between mastication and cognitive function and (2) the association between mastication and dementia incidence, in elderly people. MATERIALS AND METHODS: Searches were conducted on five electronic databases (PubMed, EMBASE, CINHL, Cochrane Library, and Pro Quest) and publications were selected that met the following criteria: published between 2005 and 2015, written in English, and assessed associations between mastication and cognitive function, cognitive decline and dementia among population over 40 years old. The included publications were analyzed for study design, main conclusions, and strength of evidence by two reviewers who screened all abstracts and full-text articles, abstracted data and performed quality assessments by using a critical appraisal tool. RESULTS: A total of 33 articles (22 cross-sectional, and 11 prospective cohort studies) were evaluated. Poorer mastication was associated with lower cognitive function in 15 of the 17 cross-sectional studies and steeper decline in 5 of the 6 prospective studies. Poorer mastication was one of significant risk factors for having dementia or mild memory impairment (MMI) in 4 of 5 cross-sectional studies and for the incidence of dementia or MMI in 4 of 5 prospective studies. CONCLUSIONS: Most studies point to a positive association between mastication and cognitive function, including dementia among elderly people.

CD56(dim)CD16(high) and CD56(bright)CD16(-) cell percentages associated with maximum knee extensor strength and incidence of death in elderly.

Physical fitness is an indicator of systemic well-being in humans. Little is known about the role of physical fitness for maintaining systemic health in the elderly. Here, we study elderly subjects to determine the relationships between physical fitness and CD56 and CD16 surface NK cell markers on peripheral blood lymphocytes, as well as to analyze the relationship between the surface markers and incidence of death. We selected 253 independent elderly subjects (122 female; 131 male) who were 79-80 years old. Subjects having a higher proportion of CD56(dim)CD16(high) within CD56(+)CD16(+) cells, or ration of CD56(dim)CD16(high) and CD56(dim)CD16(-) cells had a significant positive correlation with maximum bilateral knee extensor strength/weight (kg) (r = 0.425; P < 0.0001 or r = 0.323; P < 0.0001). In contrast, an increased proportion of CD56(bright)CD16(-) cells within lymphocyte significantly negatively correlated with the maximum bilateral knee extensor strength/weight (kg) (r = -0.290; P = 0.0004); and these subjects had a significantly lower mortality during the 5 years following measurement of death. Therefore, we found that a synergistic effect of the right and left leg muscle strength was associated with proportion of matured NK and NKT cells and induced a low proportion of CD56(bright)CD16(-) cells within lymphocyte. Moreover, the low proportion of CD56(bright)CD16(-) cells was associated with incidence of death. In conclusion, measurements of physical fitness, the proportion of CD56(dim)CD16(high) within CD56(+)CD16(+) cells, the ratio of CD56(dim)CD56(high) and CD56(dim)CD16(-) cells, and the proportion of CD56(bright)C16(-) cells in lymphocytes are important indicators to check elderly health.

Status of reduced expression and hypermethylation of the APC tumor suppressor gene in human oral squamous cell carcinoma.

The adenomatous polyposis coli gene (APC gene) originally was identified as a tumor suppressor gene in colon cancer. We reported previously that APC is mutated and/or deleted in primary oral squamous cell carcinoma (OSCC) tissues and suggested that loss of APC function contributes to carcinogenesis in the oral region. In this study, we examined 50 OSCC tissue samples, which had been fixed in 10% buffered formaldehyde solution and embedded in paraffin, and eight cell lines, which were derived from OSCC, to analyze the expression level of the APC gene. Significant down-regulation of APC was detected by immunohistochemistry in 15 (30.0%) of 50 tissue samples and by the reverse transcriptase-polymerase chain reaction in five (62.5%) of eight cell lines. We then investigated the status of APC gene promoter methylation and restoration of the APC gene mRNA. Hypermethylation of the APC promoter CpG island was detected in two of eight (25%) OSCC-derived cell lines, and APC gene mRNA was restored in all OSCC-derived cell lines showing down-regulation of gene expression (n=5) after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Thus, the contribution of down-regulated APC expression to the development of human OSCC was about 30%, and hypermethylation of the gene promoter CpG island was confirmed to be a significant mechanism of inactivation of the APC gene in oral carcinogenesis.

Percentile curves for food acceptance response scores in assessing chewing functions in adults.

The purpose of this study was to evaluate whether percentile curves for food acceptance response scores were useful in assessing oral and occlusal conditions. We used data obtained from Chiba City Patient Surveys (males: 1,276, females: 1,381, aged 20 to 64), which were conducted in 1998 and 1999. Subjects were assigned scores of between 1 and 4 for 31 different kinds of food based on their food acceptance responses. Occlusal conditions were measured with pressure-sensitive sheets. We calculated the percentile values from 5 to 95 at intervals of five years. We divided the subjects into two groups at the twenty-fifth percentile and statistically analyzed various oral conditions in the two groups. Significant differences were found between them in the mean numbers of present, sound, and missing teeth for almost all age groups. Moreover, there were significant differences in tooth-contact area and occlusal force between the two groups. The results of multiple regression analysis revealed that the scores had a stronger correlation with occlusal conditions than number of teeth in 55-year-olds, although the effect teeth-factors had on scores was more significant in 45- to 50-year-old males. Females' scores had a stronger correlation with occlusal conditions than number of teeth in all age groups. These results indicate that the questionnaire on the acceptance of 31 different kinds of food is useful in providing a basis for oral health instruction and dental treatment aimed at improving chewing ability in adults.

Factors affecting changes in compliance with infection control practices by dentists in Japan.

We surveyed compliance with infection control practices (ICPs) and factors associated with ICPs reported by dentists in Japan in 2008 and 2011. ICPs improved during this period as did the proportion of dentists specializing in oral surgery, the proportion of dentists reporting a willingness to treat HIV and AIDS patients, and the proportion of dentists reporting knowledge about universal and standard precautions. Stronger associations between ICPs and these 3 factors were found in 2011 than in 2008.