Helical peptides with disordered regions for measles viruses provide new generalized insights into fusion inhibitors.

Despite effective vaccines, measles virus (MeV) outbreaks occur sporadically. Therefore, developing anti-MeV agents remains important for suppressing MeV infections. We previously designed peptide-based MeV fusion inhibitors, M1 and M2, that target MeV class I fusion protein (F protein). Here, we developed a novel fusion inhibitor, MEK35, that exerts potent activity against M1/M2-resistant MeV variants. Comparing MEK35 to M1 derivatives revealed that combining disordered and helical elements was essential for overcoming M1/M2 resistance. Moreover, we propose a three-step antiviral process for peptide-based fusion inhibitors: (i) disordered peptides interact with F protein; (ii) the peptides adopt a partial helical conformation and bind to F protein through hydrophobic interactions; and (iii) subsequent interactions involving the disordered region of the peptides afford a peptide-F protein with a high-affinity peptide-F protein interaction. An M1-resistant substitution blocks the second step. These results should aid the development of novel viral fusion inhibitors targeting class I F protein.

Comparison of T2 values of the displaced unilateral disc and retrodiscal tissue of temporomandibular joints and their implications.

Unilateral anterior disc displacement (uADD) has been shown to affect the contralateral joints qualitatively. This study aims to assess the quantitative T2 values of the articular disc and retrodiscal tissue of patients with uADD at 1.5 Tesla (T). The study included 65 uADD patients and 17 volunteers. The regions of interest on T2 maps were evaluated. The affected joints demonstrated significantly higher articular disc T2 values (31.5 ± 3.8 ms) than those of the unaffected joints (28.9 ± 4.5 ms) (P < 0.001). For retrodiscal tissue, T2 values of the unaffected (37.8 ± 5.8 ms) and affected joints (41.6 ± 7.1 ms) were significantly longer than those of normal volunteers (34.4 ± 3.2 ms) (P < 0.001). Furthermore, uADD without reduction (WOR) joints (43.3 ± 6.8 ms) showed statistically higher T2 values than the unaffected joints of both uADD with reduction (WR) (33.9 ± 3.8 ms) and uADDWOR (38.9 ± 5.8 ms), and the affected joints of uADDWR (35.8 ± 4.4 ms). The mean T2 value of the unaffected joints of uADDWOR was significantly longer than that of healthy volunteers (P < 0.001). These results provided quantitative evidence for the influence of the affected joints on the contralateral joints.

Clear Cell Squamous Cell Carcinoma of the Maxillary Gingiva Associated with PIK3CA and HRAS Mutations: Report of a Case and Literature Review.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common oral malignancy, and somatic mutations in some driver genes have been implicated in SCC development. Clear cell SCC (CCSCC) is a rare histological variant of SCC, and various clear cell neoplasms must be considered in the differential diagnosis of CCSCC in the oral cavity. Based on a limited number of CCSCC cases reported in the oral cavity, CCSCC is considered an aggressive variant of SCC with a poor prognosis; however, its genetic characteristics remain unknown. METHODS: A maxillary gingival tumor in an 89-year-old female was described and investigated using immunohistochemical staining, special staining, fluorescence in situ hybridization, and next-generation sequencing (NGS) with a custom panel of driver genes, including those associated with SCC and clear cell neoplasm development. RESULTS: Histopathological examination revealed a proliferation of atypical epithelial cells with abundant clear cytoplasm and enlarged and centrally placed round nuclei. The tumor was exophytic with deep, penetrating proliferation. The atypical clear cells were continuous with the conventional SCC cells. Immunohistochemical analysis showed that the clear cells were positive for CK AE1/AE3 and CK5/6 and nuclear-positive for p63. In contrast, the clear cells were negative for αSMA, S100, HMB45, Melan-A, CD10, and p16. p53 immunoreactivity exhibited a wild-type expression pattern. Additionally, the clear cells were positive for periodic acid-Schiff (PAS) and negative for diastase-PAS, mucicarmine, and Alcian blue. Based on these results, the diagnosis of CCSCC was confirmed. Molecular analysis of the clear cells identified PIK3CA p.E542K (c.1624G>A) and HRAS p.G12A (c.35 G>C) somatic mutations classified as oncogenic. No pathogenic variants were identified in TP53, EWSR1, AKT1, PTEN, BRAF, KRAS, NRAS, RASA1, or MAML2. CONCLUSIONS: We report a case of CCSCC of the oral cavity with PIK3CA and HRAS mutations. The identification of PIK3CA and/or HRAS mutations is rare in SCC; however, both mutations are important potential targets for antitumor therapy. A detailed analysis of gene mutations in CCSCC may lead to a better understanding of its biological behavior and an improved prognosis, as well as a differential diagnosis from other clear cell neoplasms.

Inverse planning optimization with lead block effectively suppresses dose to the mandible in high-dose-rate brachytherapy for tongue cancer.

PURPOSE: In this study, we developed in-house software to evaluate the effect of the lead block (LB)-inserted spacer on the mandibular dose in interstitial brachytherapy (ISBT) for tongue cancer. In addition, an inverse planning algorithm for LB attenuation was developed, and its performance in mandibular dose reduction was evaluated. METHODS: Treatment plans of 30 patients with tongue cancer treated with ISBT were evaluated. The prescribed dose was 54 Gy/9 fractions. An in-house software was developed to calculate the dose distribution based on the American Association of Physicists in Medicine (AAPM) Task Group No.43 (TG-43) formalism. The mandibular dose was calculated with consideration of the LB attenuation. The attenuation coefficient of the lead was computed using the PHITS Monte Carlo simulation. The software further optimized the treatment plans using an attraction-repulsion model (ARM) to account for the LB attenuation. RESULTS: Compared to the calculation in water, the D2 cc of the mandible changed by - 2.4 ± 2.3 Gy (range, - 8.6 to - 0.1 Gy) when the LB attenuation was considered. The ARM optimization with consideration of the LB resulted in a - 2.4 ± 2.4 Gy (range, - 8.2 to 0.0 Gy) change in mandibular D2 cc. CONCLUSIONS: This study enabled the evaluation of the dose distribution with consideration of the LB attenuation. The ARM optimization with lead attenuation further reduced the mandibular dose.

MR appearance of a rare ameloblastic fibroma with formation of dental hard tissues with histopathologic correlation: a case report.

An ameloblastic fibroma with formation of dental hard tissues, which the classical name is ameloblastic fibro-odontoma (AFO), is a rare type of mixed odontogenic tumor. An 8-year-old boy was diagnosed with AFO, with an inhomogeneous high signal within the lesion shown by T2-weighted magnetic resonance imaging (MRI). Computed tomography (CT) imaging revealed a unilocular low CT value area of 24 × 19 × 26 mm with buccolingual bony expansion and cortical bone thinning on the left side of the mandible including the crown of the mandibular left second molar. In addition, multiple calcified bodies were detected within the lesion, one of which had a CT value of approximately 2200 HU, equivalent to that of enamel. MRI indicated the lesion to be sized 24 × 19 × 25 mm along with buccolingual bony expansion in the left side of the mandible. Additionally, the lesion showed an internal inhomogeneous high signal, while a portion had an especially high signal in T2-weighted images. That particularly high signal area coincided with the nodular growth area of mucus-rich mesenchymal components without the epithelial component in histopathology findings. The particularly high signal revealed by T2-weighted imaging could be attributed to the mucus-rich component. MRI was found useful for revealing differences in the internal histopathological properties of an AFO in our patient.

Radiation-induced undifferentiated spindle cell sarcoma following high-dose-rate interstitial brachytherapy for tongue squamous cell carcinoma.

High-dose-rate interstitial brachytherapy (HDR-ISBT) has recently come to be considered one of the most effective treatments for oral cancer. On the other hand, it is important to note that radiation therapy has some side effects. Especially, radiation-induced malignancy is probably the most serious complication affecting long-term survivors. We report a case of a radiation-induced undifferentiated spindle cell sarcoma that developed following HDR-ISBT for tongue squamous cell carcinoma (SCC). A 39-year-old woman with right tongue SCC underwent HDR-ISBT (60 Gy, 10 fractions, 8 days) treatment. Five years and one month later, a tumor had developed at the primary site. Surgery was performed for the tumor, which was histopathologically diagnosed as an undifferentiated spindle cell sarcoma. That was distinct from the squamous cell origin of the primary cancer. According to recently established criteria for radiation-induced malignancy, this case was classified as a radiation-induced sarcoma. A search of the literature revealed no previous report of radiation-induced malignancy following HDR-ISBT for tongue cancer.

Verbal Training Induces Enhanced Functional Connectivity in Japanese Healthy Elderly Population.

This study employs fMRI to examine the neural substrates of response to cognitive training in healthy old adults. Twenty Japanese healthy elders participated in a 4-week program and practiced a verbal articulation task on a daily basis. Functional connectivity analysis revealed that in comparison to age- and education-matched controls, elders who received the cognitive training demonstrated increased connectivity in the frontotemporal regions related with language and memory functions and showed significant correlations between the behavioral change in a linguistic task and connectivity in regions for goal-oriented persistence and lexical processing. The increased hippocampal connectivity was consistent with previous research showing efficacious memory improvement and change in hippocampal functioning. Moreover, the increased intra-network connectivity following cognitive training suggested an improved neural differentiation, in contrast to the inter-network activation pattern typical in the aging brain. This research not only validates the relationship of functional change in the frontal and temporal lobes to age-associated cognitive decline but also shows promise in turning neural change toward the right direction by cognitive training.

Multiple-echo recombined gradient echo MR imaging of the temporomandibular joint.

OBJECTIVE: The purpose of this study was to compare images generated by a multiple-echo recombined gradient echo (MERGE) with the proton density-weighted fast spin-echo (PD-weighted FSE) sequence, T1-weighted fast spin-echo sequence (T1-weighted FSE), and T2-weighted fast spin-echo sequence (T2-weighted FSE) for the diagnostic imaging of the temporomandibular joint (TMJ). MATERIALS AND METHODS: Twenty-three patients with signs and symptoms of TMJ dysfunction were enrolled in this study. The four imaging modalities were used to examine the TMJ. Three images (lateral, middle, and medial parts of the condylar head) were reviewed by two radiologists, who rated the visibility of the disk and cortex of the condylar head. RESULTS: For the medial part of the TMJ, in cases with a normally positioned disk, the results of the MERGE and PD-weighted FSE techniques were significantly better than those of the T1-weighted FSE and T2-weighted FSE. For visibility of the cortex in the normally positioned disk, MERGE was significantly better than PD-weighted FSE [P < 0.0125 (0.05/4)] at the middle and medial parts of the TMJ. MERGE was also significantly better than T1-weighted FSE [P < 0.0125 (0.05/4)] and T2-weighted FSE [P < 0.0125 (0.05/4)]. CONCLUSION: MERGE is better for visualizing the condylar only at the middle and the medial aspects of the TMJ in a normally positioned disk.

Comparison of 3-D mandibular surfaces generated by MRI and CT.

OBJECTIVE: The purpose of this study was to evaluate the errors of three-dimensional mandibular surfaces generated using magnetic resonance imaging (MRI) when computed tomography (CT) was set as the gold standard. SETTINGS AND SAMPLE POPULATION: Seven patients with orthognathic deformities who had undergone CT and MRI scans were included in the study. MATERIALS AND METHODS: Mandibular surfaces were generated on each CT and MR image by the surface-rendering method. Intra-individual reliability between CT and MRI was statistically tested by the confidence limits of agreement (LOA) for systematic error, 95% confidence interval minimal detectable change (MDC95 ) for random error and intra-class correlation coefficient (ICC). RESULTS: The average total error was 1.6 mm. The greatest MDC95 was observed in the coronoid region in all directions. The other regions showed MDC95 values of < 1.8 mm (transvers direction), 3.5 mm (vertical direction) and 1.7 mm (antero-posterior direction). ICCs showed 'almost perfect' agreement with respect to all regions. CONCLUSION: Random errors were quantified for 3-D rendering of the mandible from MRI data. Although the coronoid region showed the greatest errors, the other regions of the mandibular surfaces generated using MRI were able to be evaluated.

Prognostic factors for lymph node metastasis from upper gingival carcinomas.

OBJECTIVES: This study sought to identify tumor characteristics that associate with regional lymph node metastases in squamous cell carcinomas originating in the upper gingiva. MATERIALS AND METHODS: Data from 113 patients from Osaka University Dental Hospital were included. We measured each primary tumor's width, length, depth, and the extent of bone invasion. Additionally, tumor signal intensity for T1 and T2-weighted images as well as the center of the tumor's location and T classification was assessed, and a histopathological analysis was performed. RESULTS: Tumor signal intensity was not found to be a significant prognostic factor. However, bucco-lingual width, histopathological classification as well as the tumor's location were significantly different between metastatic and non-metastatic groups in both univariate and multivariate analysis. Superior-inferior depth and T classification were significant only in the univariate (and not the multivariate) analysis. CONCLUSIONS: Bucco-lingual width, histopathological grading as well as the tumor's location are likely to be important predictors for the occurrence of LN metastasis in upper gingival carcinoma patients and should be considered when managing care for these patients.

Primary Alveolar Soft Part Sarcoma of Cheek: Report of a Case and Review of the Literature.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma characterized by an alveolar or organoid arrangement of polygonal tumour cells separated by fibrovascular septa. A specific fusion gene [ASPS critical region 1 (ASPSCR1)-TFE3] was detected in ASPS. Despite being a slow-growing tumour without pain and dysfunction, ASPS is characterized by early metastasis, which leads to poor prognosis. Herein, we report a rare case of primary ASPS of the cheek harbouring ASPSCR1 (exon 7)-TFE3 (exon 5) fusion gene in a 21 year-old woman. This tumour was a well-circumscribed, smooth, round mass that was clinically suspected as a benign tumour. However, histologically, it was observed that the polygonal tumour cells were arranged in solid and alveolar growth patterns. Post-operative examination of the whole body excluded the possibility of metastasis at other sites. Thus, careful immunohistochemical and genetic analyses, as well as whole-body examination, demonstrated that the tumour was a primary ASPS of the cheek.

Stress increases blood beta-hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model.

AIM: This study aimed to assess the response of endogenous beta-hydroxybutyrate to psychological stress, and its association with nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome, and stress-induced behavior. METHODS: Male C57BL/6J mice were subjected to 1-hour restraint stress to examine changes in the endogenous beta-hydroxybutyrate and active NLRP3 levels in the prefrontal cortex. Subsequently, we created a depression model applying 10-day social defeat stress to the male C57BL/6J mice. RESULTS: One-hour restraint stress rapidly increased beta-hydroxybutyrate levels in the blood. The active NLRP3 levels in the prefrontal cortex also increased significantly. A correlation was found between the increased beta-hydroxybutyrate levels in the blood and the active NLRP3 levels in the prefrontal cortex. The mice exposed to social defeat stress exhibited depression- and anxiety-like behavioral changes in the open field, social interaction, and forced swim tests. There was a correlation between these behavioral changes and endogenous beta-hydroxybutyrate levels. Among the social defeat model mice, those with high beta-hydroxybutyrate levels tended to have more depression- and anxiety-like behavior. CONCLUSIONS: The increased blood beta-hydroxybutyrate levels due to psychological stress correlate with the active NLRP3 levels in the prefrontal cortex, suggesting that the increased beta-hydroxybutyrate levels due to stress may reflect a reaction to brain inflammation. In addition, mice with higher blood beta-hydroxybutyrate levels tend to exhibit increased depression- and anxiety-like behaviors; thus, an increase in blood beta-hydroxybutyrate levels due to stress may indicate stress vulnerability.

Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature.

Clear cell carcinoma (CCC) is a rare low-grade malignant salivary gland carcinoma. EWSR1-ATF1 fusion has been characterized as a consistent finding in CCC, with breakpoints described between EWSR1 exon 11 and ATF1 exon 3. So far, over 100 cases of CCC harboring EWSR1 rearrangement arising from salivary gland of the oral cavity have been reported. Although EWSR1 involvement in these cases was confirmed by EWSR1 break-apart FISH indicating the translocation, sequence analysis for EWSR1-ATF1 fusion type has been reported only in three cases of CCC so far. Herein, we report a CCC case with novel EWSR1-ATF1 fusion (EWSR1 exon 15 and ATF1 exon 5) arising in minor salivary gland and review the role of the chimeric variants in some malignancies with EWSR1-ATF1 rearrangement. Current tumor was composed of the small nests of clear tumor cells and hyalized fibrous stroma. Immunohistochemically, the tumor was positive for AE1/AE3, CK5/6 and p63, negative for S100, Melan-A, SMA and CD10. After 8 months of follow-up, there are no evidence of recurrence.

Distant metastasis from oral cavity-correlation between histopathology results and primary site.

OBJECTIVES: Oral cancer is the eighth most common type of cancer worldwide and a significant contributor to the global burden caused by this disease. The principal parameters considered to influence prognosis, and thus treatment selection, are size and location of the primary tumor, as well as assessment of the presence and extent of lymph node and distant metastasis (DM). However, no known report regarding the relationship between the primary site and DM has been presented. For effective treatment selection and good prognosis, the correlation of DM with anatomic site and histopathology results of the primary malignancy is important. In the present study, we performed a systematic review of published reports in an effort to determine the relationship between the anatomic site of various types of oral cavity cancer and DM. METHODS: A systematic review of articles published until the end of 2018 was performed using PubMed/MEDLINE. RESULTS: A total of 150 studies were selected for this review. The percentage of all cases reported with DM was 6.3%, ranging from 0.6% to 33.1% in the individual studies. The rate of incidence of tongue occurrence was 9.3%. A frequent DM site was the lungs, with adenoid cystic carcinoma the most commonly involved histopathological factor. Malignant melanoma was most frequent (43.4%) in all histopathology findings, whereas there were no cases with an acinic cell carcinoma or cystadenocarcinoma. CONCLUSIONS: We found that the occurrence of DM from the primary site as well as rate of incidence was dependent on histopathological factors.

18F-FBPA PET in Sarcoidosis: Comparison to Inflammation-Related Uptake on FDG PET.

A 68-year-old man with sarcoidosis showed high F-FDG uptake in the mediastinal and hilar lymph nodes on F-FDG PET, suggesting active inflammation. F-fluoro-boronophenylalanine (FBPA) PET showed no significant uptake in the mediastinal and hilar lymph nodes, suggesting its cancer specificity as a substrate of L-type amino acid transporter 1. F-fluoro-boronophenylalanine PET can be used for precise evaluation in oncology when the differentiation between inflammation and metastasis is inconclusive on F-FDG PET.

Diffusion-weighted magnetic resonance imaging of the oral and maxillofacial region: optimal fat suppression method.

OBJECTIVE: To compare 3 fat suppression methods-water excitation (WE), chemical shift selective (CHESS), and short T1 inversion recovery (STIR)-for optimal image quality and apparent diffusion coefficient (ADC) values with magnetic resonance imaging (MRI) using diffusion-weighted imaging (DWI) of the oral and maxillofacial region. STUDY DESIGN: In total, 53 patients with 73 lesions were enrolled in this study. MRI using DWI protocols with the 3 fat suppression methods were performed in addition to a conventional MRI protocol. The diagnostic image quality of lesions, image uniformity, degree of image artifacts, and ADC values of the lesions were evaluated. Average visual scores and ADC values were compared, and post hoc pairwise comparisons were performed, with the level of significance set at P < .0167. RESULTS: Diagnostic image quality was not significantly different among the fat suppression methods (P ≥ .042). Image uniformity was significantly higher (P < .001), and the degree of image artifacts was significantly lower (P < .001), in images using the STIR method. Mean ADC values did not differ significantly among the 3 methods. CONCLUSIONS: The STIR method was the most useful fat suppression method for DWI of the oral and maxillofacial region because of its high level of image uniformity and few image artifacts.

Comparative evaluation of bone microstructure in alveolar cleft repair by cone beam CT: influence of different autologous donor sites and additional application of ß-tricalcium phosphate.

OBJECTIVES: This study used cone beam computed tomography (CBCT) images to comparatively evaluate the three-dimensional microstructural features of reconstructed bone bridge based on the bone harvesting site and the presence/absence of artificial bone material, as well as the features of regenerated bone tissue after bone harvesting from mandibular symphysis in secondary alveolar bone grafting (SABG) for patients with cleft lip, with or without cleft palate. MATERIALS AND METHODS: Thirty-one patients were divided into three groups in which SABG was performed by autologous bone harvesting from iliac crest (IC), mandibular symphysis (MS), or MS combined with ß-TCP granules (MS+TCP). The microstructural trabecular bone parameters (TBPs) and bone structure indexes (SIs) were analyzed using datasets of CBCT images taken before and after SABG. RESULTS: TBPs showed differences between IC and MS groups (P < 0.05), resulting in greater values of bone volume density (P < 0.05) and inferior value of TBPf (P = 0.070) in IC group compared with MS group. Using MS+TCP or filling ß-TCP granules into donor site significantly improved reconstructed or regenerated BV/TV and Tb.Th (P < 0.05) compared with group without ß-TCP. CONCLUSIONS: Microstructural characteristics of reconstructed bone bridge were dependent on the donor site of bone harvesting; using an absorbable bone conductive material improved bone quality and increased bone volume density. CLINICAL RELEVANCE: Application of ß-TCP granules as a partial alternative with autologous bone from mandibular symphysis could obtain comparable outcomes in the microstructure of bone bridge to SABG with autologous iliac crest.

T2 relaxation times of the retrodiscal tissue in patients with temporomandibular joint disorders and in healthy volunteers: a comparative study.

OBJECTIVE: The aims of this study were to compare the temporomandibular joint (TMJ) retrodiscal tissue T2 relaxation times between patients with temporomandibular disorders (TMDs) and asymptomatic volunteers and to assess the diagnostic potential of this approach. STUDY DESIGN: Patients with TMD (n = 173) and asymptomatic volunteers (n = 17) were examined by using a 1.5-T magnetic resonance scanner. The imaging protocol consisted of oblique sagittal, T2-weighted, 8-echo fast spin echo sequences in the closed mouth position. Retrodiscal tissue T2 relaxation times were obtained. Additionally, disc location and reduction, disc configuration, joint effusion, osteoarthritis, and bone edema or osteonecrosis were classified using MRI scans. The T2 relaxation times of each group were statistically compared. RESULTS: Retrodiscal tissue T2 relaxation times were significantly longer in patient groups than in asymptomatic volunteers (P < .01). T2 relaxation times were significantly longer in all of the morphologic categories. The most important variables affecting retrodiscal tissue T2 relaxation times were disc configuration, joint effusion, and osteoarthritis. CONCLUSIONS: Retrodiscal tissue T2 relaxation times of patients with TMD were significantly longer than those of healthy volunteers. This finding may lead to the development of a diagnostic marker to aid in the early detection of TMDs.

Evaluation of mouthpiece fixation devices for head and neck radiotherapy patients fabricated in PolyJet photopolymer by a 3D printer.

PURPOSE: The purpose of our study was to evaluate the usefulness of a biocompatible class VI resin PolyJet photopolymer Objet MED610 (MED610)-made mouthpiece fabricated using a 3D printer as a fixation device for head and neck radiotherapy patients. METHODS: Five mouthpieces made of GC Exafine putty type (GCEP) were fabricated from five dry skull bones. After computed tomography reconstruction of the GCEP-made mouthpiece and its surface extraction, the MED610-made mouthpieces were replicated. The sizes of the GCEP and MED610 mouthpieces were measured with a vernier caliper in width, length, and height, respectively. The volumes of these mouthpieces were measured by Archimedes' principle using pure water. For dose evaluation, the GCEP and MED610 mouthpieces were placed in the same part of a water phantom, and a 4-MV X-ray beam was located at the left maxillary gingiva, buccal mucosa, and oral floor. The dose for the planning target volume (PTV) was evaluated. RESULTS: The differences in the mean size and volume between the GCEP and MED610 mouthpieces were 0.03 mm and 0.21 cm3, respectively. Compared with the conventional GCEP mouthpiece, the dose absorption in the MED610 mouthpiece was closer to that in only water. When the mouthpiece was within the PTV margin, the minimum coverage dose at 95% of the PTV increased by 2.4% in the maxillary gingiva and by 3.6% in the buccal mucosa. CONCLUSION: A 3D printer can construct a mouthpiece accurately. The MED610 mouthpiece is suitable for use in dosimetry in head and neck radiotherapy.