Periodontitis and postoperative inflammation in gastric cancer patients: Propensity score analysis.

OBJECTIVE: The objective of this study was to clarify the association between preoperative periodontitis and postoperative systemic inflammation in patients with gastric cancer. SUBJECTS AND METHODS: This retrospective cohort study analyzed data from 140 gastric cancer patients who underwent surgery at Hiroshima University Hospital between May 2019 and May 2022. Periodontal inflamed surface area (PISA) scores were determined to assess periodontitis severity using modified Nesse's methods. Propensity score matching was used to compare patients with high and low PISA scores (> or < the median PISA score of 92.4, respectively). Propensity scores were calculated using a logistic regression model, based on 17 clinical parameters: age, sex, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, cardiovascular disease, stroke, clinical stage, surgical procedure, surgical approach, neoadjuvant chemotherapy, surgery duration, blood loss during surgery, remaining teeth, and denture use. RESULTS: Thirty-seven patients were propensity-score-matched. Participants with high PISA scores had a higher incidence of surgical site infection (10.5%) than those with low PISA scores (5.3%). Moreover, participants with high PISA scores had significantly higher C-reactive protein levels on postoperative days 1 than those with low PISA scores. CONCLUSION: Preoperative periodontitis may determine the level of postoperative systemic inflammation in patients with gastric cancer.

Taste-taste associations in chemotherapy-induced subjective taste alterations: findings from a questionnaire survey in an outpatient clinic.

PURPOSE: Chemotherapy-induced taste alteration is a side effect that can result in malnutrition and reduced quality of life in cancer patients. However, the underlying causes of this phenomenon remain unclear, and evidence-based treatments have not been established. This study focused on patients' subjective symptoms of taste alterations aimed to explore how the sensitivity to basic tastes changes due to anticancer agents and how alterations in one taste perception are associated with changes in other tastes during chemotherapy. METHODS: A cross-sectional questionnaire-based interview survey was conducted on 215 patients undergoing chemotherapy. The subjective sensitivity to each basic taste was assessed using a visual analog scale, and the incidence of taste alterations due to different chemotherapy regimens was calculated. Multivariate logistic regression analysis was performed to determine whether there were associations between changes in one taste sensitivity and changes in other taste sensitivities. RESULTS: Approximately half (49.5%) of the patients experienced chemotherapy-induced taste alterations. An analysis of subjective changes in basic tastes revealed that the salt and umami taste systems were more sensitive to chemotherapy than other taste systems. Patients with altered sensitivity to sweet taste were significantly more likely to report altered sensitivity to salt, bitter, and sour tastes. Moreover, umami-salt and bitter-sour taste sensitivities were significantly related to each other. CONCLUSION: This study suggests that changes in subjective sensitivities to one basic taste during chemotherapy may be accompanied by changes in other tastes in specific combinations. Considering taste associations in dietary guidance may help improve the nutritional status of cancer patients experiencing taste alterations due to chemotherapy.

ACE2 expression and spike S1 protein-mediated immune responses in oral mucosal cells.

OBJECTIVES: ACE2, known as a host receptor involved with SARS-CoV-2 infection, binds to viral spike proteins for host cell entry. However, details regarding its induction and function in oral mucosal cells remain unknown. MATERIALS AND METHODS: We examined ACE2 expression and its induction by transfected mimic nucleotides and pro-inflammatory cytokines in oral keratinocytes (RT7) and fibroblasts (GT1). Subsequently, the effects of viral spike S1 protein via ACE2 on CXCL10 expression induced by pro-inflammatory cytokines in both cells were examined. RESULTS: ACE2 was constitutively expressed in RT7 and GT1. Transfected Poly(I:C) and Poly(dA:dT) increased ACE2 expression in those cells, while knockdown of RIG-I decreased ACE2 expression induced by those transfected ds nucleotides. IFN-γ and TNF-α enhanced transfected ds nucleotides-induced ACE2 expression in RT7 but not GT1. S1 protein alone did not affect CXCL10 expression in either cell type, whereas it enhanced IFN-ß-induced CXCL10 in both, while immune responses of IFN-γ- and TNF-α-induced CXCL10 enhanced by S1 protein were different between RT7 and GT1. Finally, knockdown of ACE2 decreased cytokines and S1 protein mediated-CXCL10 levels in both cells. CONCLUSIONS: ACE2 in oral mucosal cells may contribute to development of infection and inflammation in cooperation with pro-inflammatory cytokines following SARS-CoV-2 invasion.

Head and neck cancer patients show poor oral health as compared to those with other types of cancer.

PURPOSE: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. METHODS: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. RESULTS: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. CONCLUSION: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis.

Immune response to cytosolic DNA via intercellular receptor modulation in oral keratinocytes and fibroblasts.

OBJECTIVE: Double-strand (ds) DNA-enveloped viruses can cause oral infection. Our aim is to investigate whether oral mucosal cells participate in immune response against cytosolic dsDNA invasion. METHODS: We examined the response to transfected herpes simplex virus (HSV) dsDNA via intracellular receptors in oral keratinocytes (RT7) and fibroblasts (GT1), and the effect of TNF-α on those responses. RESULTS: Transfected dsDNA increased CXCL10 expression via NF-κB activation in both cell types, while those responses were inhibited by knockdown of RIG-I, an RNA sensor. Although IFI16, a DNA sensor, was expressed in the nuclei of both types, its knockdown decreased transfected dsDNA-induced CXCL10 expression in GT1 but not RT7 cells. IFI16 in GT1 cells was translocated into cytoplasm from nuclei, which was attributed to immune response to cytosolic dsDNA. TNF-α enhanced transfected dsDNA-induced CXCL10, and knockdown of IFI16 decreased TNF-α and dsDNA-driven CXCL10 expression in both RT7 and GT1 cells. Finally, the combination of TNF-α and transfected dsDNA resulted in translocation of IFI16 from nuclei to cytoplasm in RT7 cells. CONCLUSION: RIG-I and IFI16 in oral mucosal cells may play important roles in host immune response against DNA viral infection, while TNF-α contributes to development of an antiviral system via those intracellular receptors.

Sunitinib promotes apoptosis via p38 MAPK activation and STAT3 downregulation in oral keratinocytes.

OBJECTIVE: Sunitinib, a targeted cancer drug, inhibits tyrosine kinases receptors and is widely used as first-line treatment for metastatic renal cell carcinoma. Patients undergoing chemotherapy with sunitinib frequently have oral mucosal complications, such as oral stomatitis, though cytotoxic effects of the drug on oral keratinocytes remain unknown. METHODS: The effects of sunitinib on immortalized oral keratinocytes, RT7 cells, in regard to cell injury and apoptosis, as well as apoptosis-mediated signaling pathways were investigated. RESULTS: Sunitinib treatment caused a significant increase in lactate dehydrogenase (LDH) in RT7 cells and primary oral keratinocytes. Additionally, the drug induced apoptosis-related events, such as DNA fragmentation, decreased anti-apoptotic Bcl-2 protein expression, and induction of cleaved PARP and caspase 3/9 in RT7 cells. Furthermore, phosphorylation of p38 MAPK, but not of ERK or JNK, was increased. On the contrary, constitutive phosphorylated STAT3 was decreased by sunitinib treatment, which was recovered by exposure to SB203580, a p38 MAPK inhibitor. Finally, SB203580 was found to reduce sunitinib-induced cell injury and apoptosis. CONCLUSION: The present results indicate that sunitinib promotes cell injury and apoptosis in oral keratinocytes via p38 activation and STAT3 downregulation. Sunitinib-mediated oral complications may be associated with cytotoxic effects of the drug on oral keratinocytes.

Assessment of Serum IgG Titers to Various Periodontal Pathogens Associated with Atrial Fibrillation in Acute Stroke Patients.

OBJECTIVES: There is accumulating evidence that periodontal disease is associated with atrial fibrillation (AF) or stroke, but it is unclear which causative species of periodontal disease are present in stroke patients with AF. We aimed to investigate the associations between AF and specific periodontal pathogens using serum titers of IgG antibodies of bacteria in acute stroke patients. MATERIALS AND METHODS: Acute stroke patients were registered at two hospitals. Serum samples were evaluated for titers of antibodies against 9 periodontal pathogens (16 genotypes) using ELISAs. We identified AF in patients according to the following criteria: (1) a history of sustained or paroxysmal AF or (2) AF detection upon arrival or during admission. We carried out propensity score matching to categorize the patients as those with AF and those without. RESULTS: Of the 664 acute stroke patients, 123 (18.5%) had AF. After propensity score matching, 234 patients were selected. Patients with AF had a higher prevalence of positive serum titers of antibodies against Porphyromonas gingivalis (FimA type III) and Porphyromonas gingivalis (FimA type V) than those without AF (59.0% vs. 39.3%, p=0.004 and 58.2% vs. 40.2%, p=0.009, respectively). CONCLUSIONS: Porphyromonas gingivalis, especially FimA type III and type V, might be associated with AF in stroke patients.

Periodontitis and the outcome of atrial fibrillation ablation: Porphyromonas gingivalis is related to atrial fibrillation recurrence.

INTRODUCTION: Inflammation is one of the main causes of atrial fibrillation (AF) recurrence after ablation. Porphyromonas gingivalis is a key periodontal pathogen in the oral-systemic disease connection and serum immunoglobulin G (IgG) antibody titers against P. gingivalis reflect the clinical status of periodontitis. This study aimed to investigate the relationship between late recurrence of AF after radiofrequency catheter ablation (RFCA) and serum IgG antibody titers against P. gingivalis. METHODS: A total of 596 AF patients (mean age, 64.9 ± 10.0 years; 69% male; 61% paroxysmal AF) who underwent a first session of RFCA were enrolled. Patients were carefully examined for late recurrence during a mean follow-up period of 17.1 ± 14.5 months. Serum IgG antibody titers against P. gingivalis (types I-IV) were measured using enzyme-linked immunosorbent assay. The results of serum antibody titers were divided into a high-value and a low-value group. RESULTS: Among the five P. gingivalis subtypes, serum antibody titer against P. gingivalis type IV was associated with late recurrence (odds ratio, 1.937; 95% confidence interval [CI], 1.301-2.884; p = .002). Multivariate Cox proportional-hazards regression analysis revealed that high-value serum antibody titer against P. gingivalis type IV independently predicted late recurrence (paroxysmal AF: adjusted hazard ratio [HR], 1.569; 95% CI, 1.010-2.427; p = .04; non-paroxysmal AF: adjusted HR, 1.909; 95% CI, 1.213-3.005; p = .004). CONCLUSION: Periodontitis was related to the late recurrence of AF after RFCA. P. gingivalis type IV may be pathogenic for AF recurrence after RFCA.

Effects of perioperative oral care on postoperative inflammation following heart valve surgery.

OBJECTIVE: Whether oral health care during the perioperative period can lead to a better outcome after heart valve surgery has not been adequately elucidated. We examined the effects of perioperative oral care on postoperative inflammation response in patients who underwent heart valve surgery. MATERIALS AND METHODS: In this retrospective cohort study, 223 patients scheduled for single valve heart surgery were divided into the oral care, who underwent professional teeth cleaning or scaling within 3 days prior to surgery, and also following surgery at least twice a week (n = 111), and non-oral care (n = 112) groups. After propensity score matching, records of both groups (80:80) were examined after surgery to evaluate inflammation markers (white blood cell count [WBC], neutrophil/white blood cell ratio [NWR], C-reactive protein [CRP] level, body temperature [BT]). RESULTS: WBC, NWR, CRP level, and BT were increased in both groups the day following surgery. Thereafter, CRP level, WBC, NWR, and BT on various days after surgery in the oral care group showed greater decreases as compared to the non-oral care group. CONCLUSIONS: Perioperative oral health care can decrease postoperative inflammation in patients undergoing heart valve surgery and may be important to ensure a better outcome in those patients.

Candida albicans ß-Glucan-Containing Particles Increase HO-1 Expression in Oral Keratinocytes via a Reactive Oxygen Species/p38 Mitogen-Activated Protein Kinase/Nrf2 Pathway.

Oral keratinocytes provide the first line of host defense against oral candidiasis. We speculated that interactions of fungal cell wall components with oral keratinocytes regulate the stress response against Candida infection and examined the expression of genes induced by heat-killed Candida albicans in oral immortalized keratinocytes using a cDNA microarray technique. Of 24,000 genes revealed by that analysis, we focused on HO-1, a stress-inducible gene, as its expression was increased by both heat-killed and live C. albicans In histological findings, HO-1 expression in the superficial layers of the oral epithelium following Candida infection was elevated compared to that in healthy epithelium. We then investigated fungal cell wall components involved in induction of HO-1 expression and found that ß-glucan-containing particles (ß-GPs) increased its expression. Furthermore, ß-glucan was observed on the surface of both heat-killed C. albicans and Candida cells that had invaded the oral epithelium. Fungal ß-GPs also promoted induction of intracellular reactive oxygen species (ROS), NADPH oxidase activation, and p38 mitogen-activated protein kinase (MAPK) phosphorylation, while those specific inhibitors inhibited the HO-1 expression induced by fungal ß-GPs. Moreover, fungal ß-GPs induced Nrf2 translocation into nuclei via p38 MAPK signaling, while the HO-1 expression induced by fungal ß-GPs was inhibited by Nrf2-specific small interfering RNA (siRNA). Finally, knockdown of cells by HO-1- and Nrf2-specific siRNAs resulted in increased ß-GP-mediated ROS production compared to that in the control cells. Our results show that the HO-1 induced by fungal ß-GPs via ROS/p38 MAPK/Nrf2 from oral keratinocytes may have important roles in host defense against the stress caused by Candida infection in the oral epithelium.

Expression and function of RIG-I in oral keratinocytes and fibroblasts.

BACKGROUND: Innate immune response by oral mucosal cells may be the first line of host defense against viral infection. Retinoic acid-inducible gene-I (RIG-I) recognizes viral dsRNA in the cytoplasm, and RIG-I-mediated signaling regulates antiviral type I IFN, and inflammatory chemokine production. Here, we tested the hypothesis that oral mucosal cell participation in host defense against viral infection via RIG-I. METHODS: RIG-I expression was detected in immortalized oral keratinocytes (RT7), oral fibroblasts (GT1) using and RT-PCR and immunohistochemistry. RT7 and GT1 were exposed to dsRNA virus mimic Poly I:C-LMW/LyoVec (PLV). Expression of IFN-ß and CXCL10 via RIG-I was examined by Real-time RT-PCR and ELISA. Phosphorylation of IRF3 and STAT1 were detected by western blotting. RESULTS: RT7 and GT1 constitutively expressed RIG-I in the cytoplasm. Furthermore, PLV increased IFN-ß and CXCL10 productions in both RT7 and GT1 via RIG-I concurrent with phosphorylation of IRF3 and STAT1. PLV-induced CXCL10 production was attenuated by neutralization of IFN-ß and blocking of IFN-α/ß receptor (IFNAR), indicating primal IFN-ß production via the RIG-I-IRF3 axis, which eventually induces CXCL10 production via the IFNAR -STAT1 axis. CONCLUSION: We propose that RIG-I in oral keratinocytes and fibroblasts may cumulatively develop host-defense mechanisms against viral infection in oral mucosa.

Effect of Periodontal Treatment on Reducing Chronic Inflammation in Systemically Healthy Patients With Periodontal Disease.

BACKGROUND: We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in systemically healthy individuals with periodontal disease. METHODS: This multicenter study included systemically healthy individuals with periodontal disease who received initial periodontal treatment and had no periodontal treatment history. Periodontal parameters, including periodontal inflamed surface area, masticatory efficiency, and periodontal disease classification; serum IL-6 and HsCRP levels; and serum immunoglobulin (Ig)G titers against periodontal pathogens were evaluated at baseline and after treatment. Subjects were classified as low or high responders (group) based on periodontal inflamed surface area changes. RESULTS: There were 153 participants. Only periodontal inflamed surface area changes were markedly different between low and high responders. Periodontal treatment (time point) decreased both serum IL-6 and HsCRP levels. The interaction between group and time point was remarkable only for serum IL-6 levels. Changes in serum immunoglobulin (Ig)G titers against periodontal pathogens were not associated with IL-6 changes in high responders. We analyzed the indirect effect of serum anti-Porphyromonas gingivalis type 2 IgG titer changes using mediation analysis and found no significance. However, the direct effect of group (low or high responder) on IL-6 changes was considerable. CONCLUSIONS: Periodontal treatment effectively decreased serum IL-6 levels, independent of periodontal pathogen infection, in systemically healthy individuals with periodontal disease.

Relationship of oral bacterial number with medical hospitalization costs in analysis of Diagnosis Procedure Combination database from single institution in Japan.

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs.

Interleukin-8 and CXCL10 expression in oral keratinocytes and fibroblasts via Toll-like receptors.

Oral keratinocytes and fibroblasts may be the first line of host defense against oral microorganisms. Here, the contention that oral keratinocytes and fibroblasts recognize microbial components via Toll-like receptors (TLRs) and participate in development of oral inflammation was examined. It was found that immortalized oral keratinocytes (RT7), fibroblasts (GT1) and primary cells express mRNA of TLRs 1-10. Interleukin-8 (IL-8) production by RT7 cells was induced by treatment with TLRs 1-9 with the exception of TLR7 agonist, whereas GT1 cells were induced to produce IL-8 by all TLR agonists tested except for TLR7 and TLR9. GT1 cells showed increased CXCL10 production following treatment with agonists for TLR1/2, TLR3, TLR4, and TLR5, whereas only those for TLR3 and TLR5 increased CXCL10 production in RT7 cells. Moreover, TLR agonists differentially regulated tumor necrosis factor-alpha-induced IL-8 and CXCL10 production by the tested cell types. These findings suggest that recognition of pathogenic microorganisms in oral keratinocytes and fibroblasts by TLRs may have important roles in orchestrating host immune responses via production of various chemokines.

LL-37-dsRNA Complexes Modulate Immune Response via RIG-I in Oral Keratinocytes.

Recognition of nucleic acids as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) promotes an inflammatory response. On the other hand, LL-37, an antimicrobial peptide, is a multifunctional modulator of immune response, though whether it modulates inflammatory responses induced by nucleic acids in oral keratinocytes is unknown. In this study, we firstly investigated the effect of LL-37 on CXCL10 induced by DAMPs and PAMPs in immortalized oral keratinocytes, RT7. Furthermore, the effects of LL-37 on translocation of exogenous nucleic acids into cytoplasm as well as cytosolic receptor, RIG-I on immune responses mediated by LL-37-nucleic acid complexes were examined. From these results, LL-37 enhanced necrotic cell supernatant (NCS)-induced CXCL10 expression in RT7, while the response was decreased by RNase. Complexes of LL-37 and double-stranded (ds) RNA, Poly(I:C) enhanced CXCL10 expression in comparison with each alone, which were associated with NF-κB activation. Furthermore, LL-37 was shown to bind with ds nucleotides and translocate into cytoplasm. Knockdown of RIG-I decreased expression of CXCL10 induced by LL-37-Poly(I:C) complexes, and RIG-I were co-localized with Poly(I:C) entered by LL-37 in cytoplasm. LL-37 modulates dsRNA-mediated inflammatory response via RIG-I in oral keratinocytes, which may play an important role in the pathogenesis of oral inflammatory diseases.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

PURPOSE: Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. METHODS: A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. RESULTS: The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106 CFU/mL, cycle 3: 4.61 × 106 CFU/mL, cycle 4: 5.85 × 106 CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. CONCLUSION: FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

Different CprABC amino acid sequences affect nisin A susceptibility in Clostridioides difficile isolates.

Clinical isolates of Clostridioides difficile sometimes exhibit multidrug resistance and cause diarrhea after antibiotic administration. Metronidazole and vancomycin are often used as therapeutic agents, but resistance to these antibiotics has been found clinically. Therefore, the development of alternative antimicrobial agents is needed. Nisin A, produced by Lactococcus lactis, has been demonstrated to be effective against C. difficile infection. In this study, we evaluated the susceptibility of 11 C. difficile clinical isolates to nisin A and found that they could be divided into 2 groups: high and low susceptibility. Since CprABC and DltDABC, which are responsible for nisin A efflux and cell surface charge, respectively, have been reported to be related to nisin A susceptibility, we investigated the expression of cprA and dltA among the 11 strains. cprA expression in all strains was induced by nisin A, but dltA expression was not. The expression levels of both genes did not correlate with nisin A susceptibility in these clinical isolates. To evaluate cell surface charge, we performed a cytochrome C binding assay and found no relationship between charge and nisin A susceptibility. Then, we determined the whole genome sequence of each clinical isolate and carried out phylogenetic analysis. The 11 isolates separated into two major clusters, which were consistent with the differences in nisin A susceptibility. Furthermore, we found common differences in several amino acids in the sequences of CprA, CprB, and CprC between the two clusters. Therefore, we speculated that the different amino acid sequences of CprABC might be related to nisin A susceptibility. In addition, C. difficile strains could be divided in the same two groups based on susceptibility to epidermin and mutacin III, which are structurally similar to nisin A. These results suggest that genotypic variations in C. difficile strains confer different susceptibilities to bacteriocins.

Relationship Between Periodontitis and Atrial Fibrosis in Atrial Fibrillation: Histological Evaluation of Left Atrial Appendages.

BACKGROUND: Atrial fibrosis contributes to the onset and persistence of atrial fibrillation (AF) and AF-related stroke. Periodontitis, a common infectious and inflammatory disease, aggravates some systemic diseases. However, the association of periodontitis with AF and with atrial fibrosis has remained unclarified. OBJECTIVES: The authors aimed to elucidate the relationship between periodontitis and atrial fibrosis by studying resected left atrial appendages (LAAs). METHODS: Seventy-six patients with AF (55 with nonparoxysmal AF, 25 with mitral valve regurgitation, 18 with LAA thrombus) who were scheduled to undergo LAA excision during cardiac surgery were prospectively enrolled. All patients underwent an oral examination, and the remaining number of teeth, bleeding on probing, periodontal probing depth, and periodontal inflamed surface area (PISA) were evaluated as parameters of periodontitis. The degree of fibrosis in each LAA was quantified by Azan-Mallory staining. RESULTS: Bleeding on probing (R = 0.48; P < 0.0001), periodontal probing depth of ≥4 mm (R = 0.26; P = 0.02), and PISA (R = 0.46; P < 0.0001) were positively correlated with atrial fibrosis. Among patients with >10 remaining teeth, PISA was positively and strongly correlated with atrial fibrosis (R = 0.57; P < 0.0001). After adjustments for age, AF duration, BMI, mitral valve regurgitation, and CHADS2 (congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack) score, PISA was significantly associated with atrial fibrosis (ß = 0.016; P = 0.0002). CONCLUSIONS: The authors histologically revealed the association of periodontitis with atrial fibrosis. This indicates that periodontitis, which is modifiable, is likely a risk factor for AF.

Efficacy of Low-Level Laser Therapy for Oral Mucositis in Hematologic Patients Undergoing Transplantation: A Single-Arm Prospective Study.

Oral mucositis significantly affects the quality of life in hematologic cancer patients undergoing hematopoietic stem cell transplantation. Despite global evidence supporting the efficacy of low-level laser therapy (LLLT) for mucositis prevention, its clinical adoption in Japan is limited. This study aimed to fill this gap by evaluating the safety and efficacy of LLLT in a Japanese patient population. In a single-group, non-blinded, exploratory trial, we compared 21 LLLT-treated patients against a historical control of 96 patients. The primary endpoint was the incidence of Grade ≥ 2 mucositis, based on NCI-CTCAE ver. 4.0. The LLLT group showed a significantly lower incidence of Grade ≥ 2 mucositis (23.8%) compared to the control group (64.6%) (p = 0.0006). Furthermore, Grade ≥ 2 mucositis correlated with increased oral dryness and longer hospital stays. Our study confirms the efficacy of LLLT in reducing the onset of severe oral mucositis among Japanese hematologic cancer patients, advocating for its clinical introduction as a preventive measure in Japan.

Two PARP13 isoforms are associated with induction of antiviral factors in oral mucosal cells.

Innate immune systems in the oral cavity have important roles in the host defense against viral invasion of oral mucosa. Poly(ADP­ribose) polymerase 13 (PARP13), which has a strong antiviral ability, has been reported to possess two isoforms; a full­length protein, zinc­finger antiviral protein long (ZAPL), and a shorter protein (ZAPS). However, the expression and function of these two isoforms in oral mucosa remain unknown. In the present study, the expression levels of ZAPL and ZAPS induced by transfected double­stranded (ds) RNA, Poly(I:C), and dsDNA, Poly(dA:dT), in immortalized oral keratinocytes and fibroblasts (RT7 and GT1 cell lines, respectively) were investigated. Subsequently, the effects of the knockdown of ZAPL and ZAPS on transfected nucleotide­induced antiviral factors were examined. The results demonstrated constitutive expression of ZAPL and ZAPS in RT7 and GT1 cells, and their expression in both cell types was notably increased by transfection of Poly(I:C) and Poly(dA:dT) when compared with no transfection. Specific knockdown of ZAPL and ZAPS in RT7 cells decreased IFN­ß and C­X­C motif chemokine ligand 10 (CXCL10) expression induced by transfected Poly(I:C) and Poly(dA:dT). On the other hand, knockdown of ZAPL and ZAPS in GT1 cells decreased the expression of CXCL10 induced by the transfected nucleotides, whereas that had no effect on IFN­ß expression induced by Poly(dA:dT). Their knockdown was also associated with transfected nucleotides­induced IFN regulatory factor 3 phosphorylation in both cell types. Taken together, these results indicate that ZAPL and ZAPS, isoforms of PARP13, in oral mucosal cells participate in host defense against viral infection of oral mucosa.