odontogenic infection of Porphyromonas gingivalis (P.g.), a major periodontal pathogen, exacerbates pathological progression of non-alcoholic steatohepatitis (NASH). In this study, we aimed to clarify the detailed mechanism in which P.g. induced hepatic stellate cells (HSCs; key effector cells in liver fibrosis) activation. In the liver of high fat diet-induced NASH mouse model with P.g. odontogenic infection, immunolocalization of P.g. was detected. The number of hepatic crown-like structure, which was macrophage aggregation and related to liver fibrosis, was drastically increased and fibrosis area was also increased through upregulating immunoexpression of Phosphorylated Smad2 (key signaling molecule of TGF-β1) and Galectin-3. P.g.-secreted trypsin-like enzyme [gingipain; an activator of protease-activated receptor 2 (PAR2)] stimulated HSC proliferation and differentiation through Smad and ERK signaling induced by TGF-β1 produced from HSCs with P.g.-infection. Further, Galectin-3 produced from HSCs with P.g. infection and P.g.-derived LPS/lipoprotein stimulation stabilized TGFβ-receptor II resulting in increasing sensitivity for TGF-β1, finally leading to HSC differentiation via activating Smad and ERK signaling. In addition to them, hepatocytes (main component cells of liver) contributed to HSC activation through TGF-β1 and Galectin-3 production in paracrine manner. Collectively, P.g.-odontogenic infection exacerbates fibrosis of NASH by HSC activation through TGF-β1 and Gal-3 production from HSCs and hepatocytes.Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatic disease caused by obesity including simple steatosis and non-alcoholic steatohepatitis (NASH). The morbidity rate of NAFLD is high, up to 30% in Western countries, with increasing the number of NAFLD patients because of the increase of obesity 1-3 . Most NAFLD patients indicate simple steatosis, which is a reversible condition, but 10-20% of simple steatosis progresses to NASH, which is presented as inflammation with hepatocyte degeneration followed by hepatic fibrosis 3 . As some of the NASH cases eventually result in liver cirrhosis and cancer, it is a critical health problem requiring adequate prevention and early therapeutic intervention 2,4 . The mechanisms for the development and progression of NASH are extremely complicated. Recently, it was reported that fat deposition, inflammation and fibrosis in NASH are simultaneously caused by many factors such as up-regulation of free fatty acids (FFA), oxidation stress, cytokines and bacterial lipopolysaccharide (LPS) 5 .Porphyromonas gingivalis (P.g.) is a main periodontal pathogen. Periodontitis caused by P.g. is a well-recognized risk factor for many systemic diseases such as cardiovascular disease, preterm birth, diabetes mellitus, and rheumatoid arthritis 6-9 . P.g. can enter the blood circulation from periodontal disease sites and disseminate into the whole body and it can be detected in the distant organs including liver 6,7,10,11 . Furusho et al. reported that P.g.-odontogenic infect...

BACKGROUND:The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk-stratification reporting system that was introduced in 2018. The objective of this multi-institutional study was to evaluate the utility of the MSRSGC in Japan. METHODS: In total, 1608 fine-needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses. RESULTS: The cases were classified as follows: nondiagnostic, 18.1%; non-neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm-benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non-neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm-benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky-stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non-neoplastic category. CONCLUSIONS:The MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan. Cancer Cytopathol 2021;0:1-11.

Abstract:The reverberation time in a room with unevenly distributed sound absorbers, such as a room having an absorptive floor and/or ceiling, is often observed to be longer in the middle-and highfrequency ranges than the values obtained using the Sabine/Eyring formula. In the present study, this phenomenon was investigated through a scale-model experiment and three-dimensional wave-based numerical analysis. The reverberation time in a room having an absorptive floor and/or ceiling was verified to be longer in the middle-and high-frequency ranges, and the arrangement of absorbers was found to affect the frequency characteristic of the reverberation time. The increase in the reverberation time is caused by the slow decay of the axial and tangential modes in the horizontal direction. The reverberation time is longer in the high-frequency range (in which the wavelength is sufficiently shorter compared with the height of the ceiling) than in the low-frequency range, even when the frequency characteristics of the absorption coefficients of the absorbers are flat. As a means of improving such an uneven reverberation time in a room, both the placement of diffusers in the vertical direction and the use of inwardly inclined walls (in rooms with highly absorptive floors) have been found to be effective.

Dental infection is risk for preterm birth (PTB) through unclear mechanisms. We established a dental infection-induced PTB mouse model, in which Porphyromonas gingivalis (P.g.) induced PTB by 2 days. We analysed pathogenic factors contributing to PTB and their effects on trophoblasts in vitro. TNF-α, IL-8, and COX-2 were upregulated in P.g.-infected placenta. Galectin-3 (Gal-3), an immune regulator, was significantly upregulated in placenta, amniotic fluid, and serum. In vitro, P.g.-lipopolysaccharide (P.g.-LPS) increased TNF-α and Gal-3 in trophoblasts via NF-κB/MAPK signalling. Gal-3 inhibition significantly downregulated P.g.-LPS-induced TNF-α production. TNF-α upregulated Gal-3. Gal-3 also increased cytokines and Gal-3 through NF-κB/MAPK signalling. Moreover, Gal-3 suppressed CD-66a expression at the maternal-foetal interface. Co-stimulation with Gal-3 and P.g.-LPS upregulated cytokine levels, while Gal-3 plus Aggregatibacter actinomycetemcomitans (A.a.)- or Escherichia coli (E. coli)-LPS treatment downregulated them, indicating the critical role of Gal-3 especially in P.g. dental infection-induced PTB. P.g.-dental infection induced PTB, which was associated with Gal-3-dependent cytokine production. New therapies and/or diagnostic systems targeting Gal-3 may reduce PTB.

Aim: Non-alcoholic steatohepatitis (NASH) is a critical liver disease showing potential progression to liver cirrhosis/cancer. Previously, we had reported that odontogenic infection of Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, exacerbates fibrosis in NASH through the production of fibrosis mediators such as transforming growth factor-β1 (TGF-β1) and galectin-3. In this study, we determined the effects of therapeutic interventions using antibiotics on NASH progression induced by P. gingivalis odontogenic infection.Materials and methods: To eliminate P. gingivalis infection, the macrolide antibiotic [azithromycin (AZM)] was applied locally and/or systemically to a high-fat-dietinduced NASH mouse model with P. gingivalis odontogenic infection. After treatment with AZM, liver and periodontal tissues were analysed with focus on inflammation markers such as tumour necrosis factor-α (TNF-α)/Tnf-α and interleukin-1β (IL-1β)/ Il-1β, and fibrosis markers such as galectin-3, phosphorylated Smad2 (pSmad2; key signalling molecule of TGF-β1), and the number of hepatic crown-like structures (hCLSs). Further, Non-alcoholic Fatty Liver Disease Activity Score (NAS), a common histological scoring system, and fibrosis area were evaluated. Results: P. gingivalis odontogenic infection significantly increased the expression ofTnf-α, Il-1β, galectin-3, and pSmad2, the number of hCLSs, and NAS score, whereas the elimination of P. gingivalis odontogenic infection, especially local with or without systemic application, significantly inhibited them. Conclusion:This study suggests that elimination of P. gingivalis odontogenic infection inhibited NASH progression induced by the infection.

Central mucoepidermoid carcinoma (MEC) poses a diagnostic challenge because of its rarity and histological overlap with glandular odontogenic cyst (GOC). In MEC of both salivary glands and jaws, MAML2 arrangement has been well known as the specific gene alteration. We report a case of central MEC arising from GOC diagnosed by MAML2 fusion gene. A 57-year-old male presented a multilocular cystic lesion in left molar region of the mandible. Histopathologically, multiple cysts lined by thin cuboidal or non-keratinized squamous epithelium with small ductlike structures, mucous cells and ciliated cells were present. It was diagnosed as GOC. The recurrent lesion after nine years showed the proliferation of many cystic and solid nests composed of epidermoid, mucous and intermediated cells. Nested PCR revealed CRTC3-MAML2 fusion gene in the recurrent lesion, but not in the primary one. Similarly, MAML-2 rearrangement by FISH analysis was positive in the recurrent lesion, while negative for the primary one, thus confirming the diagnosis of central MEC arising from GOC. Analysis of MAML2 rearrangement can be used as a supportive evidence to distinguish central MEC from GOC.

Background In this study, we aimed to investigate the relationships between histopathological and intraoral ultrasonographic (IUS) findings in patients with tongue cancer. Methods IUS and histopathological findings in 46 patients with tongue cancer were considered for this study. We assessed the relationships between IUS findings regarding tumor thickness, margin type, border type, and internal echo intensity; internal/peripheral Doppler findings; and muscle invasion and histopathological findings regarding tumor thickness, differentiation, Yamamoto–Kohama (YK)‐classification grade, blood vessel invasion, lymphatic invasion, perineural invasion, and muscle invasion. Results Statistical associations were found between the following findings: between thickness determined through IUS measurement and that determined through histopathological measurement, between the IUS findings regarding tumor margin and border types and the histopathologically determined YK‐classifications grades, and between a Doppler image of the internal area of tongue lesions and lymphatic invasion. Conclusions IUS findings may be used to predict histopathological findings about tumor thickness and YK‐classification grades.

Liposarcoma (LS) is the most common soft-tissue sarcoma. Dedifferentiated liposarcoma (DDLS) shows more aggressive biological behavior than that of well-differentiated liposarcoma (WDLS), so advanced therapeutic agents based on molecular mechanism are urgently needed. Here we show that tissue inhibitors of metalloproteinases (TIMPs) from TIMP-1 to TIMP-4 are differently expressed and regulate yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) in LS. Database analysis showed high TIMP-1 expression in DDLS patients correlating with poor prognosis, but high TIMP-4 expression in WDLS patients with better prognosis. Stable TIMP-1 knockdown inactivated YAP/TAZ and inhibited proliferation, colony formation and migration in DDLS cells, which was rescued by a constitutive active YAP. However, stable overexpression of TIMP-1 showed the opposite in WDLS cells. Stable TIMP-4 knockdown activated YAP/TAZ and promoted proliferation and migration in WDLS cells, which was suppressed by YAP/TAZ inhibitor (verteporfin) or knockdown of YAP/TAZ. Recombinant TIMP-4 showed opposite results in DDLS cells. These results indicate that dedifferentiation in LS shifts the expression of TIMPs from type 4 to type 1, inducing more aggressive behavior and poor prognosis through YAP/TAZ activation, which can be prognostic markers and therapeutic targets for LS patients.