To clarify the relationship between the perceptual diagnoses of hypernasality and its physical correlates, we conducted three experiments using the Japanese vowel /i/. We performed a spectral analysis of hypernasality on five cleft palate patients and six velum resection patients to investigate the spectral features related to hypernasality (experiment 1). Psychoacoustic experiments were conducted using various spectrally modified vowels to investigate the relationships between the spectral features and auditory perceptions of hypernasality (experiment 2). We analyzed the estimated spectral envelopes using an articulatory speech synthesis model to clarify the relationship between the spectral features and the velopharyngeal opening (experiment 3). Experiments 1 and 2 suggested four spectral features as the characteristics of hypernasality: (1) broadening of the F1 bandwidth, (2) an additional peak at around 1 kHz [P1], (3)^* a decrease in the magnitude of F2, and (4)^* a dip between F2 and F3 [D2]. In particular, the simultaneous modification of the decrease in the magnitudes of F2 and D2 is a very important cue for the auditory perception of hypernasality. Experiment 3 showed that the dips caused by nasal coupling resulted in the spectral modifications. In addition, the dip regions appeared to spread from the low-frequency region (around F1) to the high-frequency region (above F2), as the velopharyngeal opening enlarged. This suggests that the decrease in the magnitude of F2 and the dip between F2 and F3 [D2] are related to excessive acoustic coupling of the nasal cavity.^* New findings.

Objectives: To investigate renal function during denosumab therapy using the estimated glomerular filtration rate based on cystatin C (eGFRcys) which is more accurate than creatinine (eGFRcr) for renal function. Methods: Bone mineral densities (BMDs) of lumbar spine and hip regions, eGFRcys, eGFRcr, creatinine clearance (Ccr), and serum total homocysteine (S-Hcy) were measured during 2-year denosumab therapy in 53 women with osteoporosis naïve to anti-osteoporosis drugs (new group) and 64 women who were switched from long-term bisphosphonate treatment to denosumab therapy (switch group). Results: There were no significant differences in age, eGFRcr, Ccr, eGFRcys, and S-Hcy levels at baseline between the groups. BMDs in the lumbar spine, femoral neck, and total hip increased significantly after 2-year denosumab therapy in both groups. eGFRcr decreased in the switch group, and Ccr decreased in both groups; however, eGFRcys and S-Hcy levels did not change significantly in either group. To investigate the causal factors associated with the decrease in eGFRcr and Ccr, multiple regression analysis was performed in all patients. Denosumab initiation within 3 months after fracture and eGFRcr or Ccr at baseline were independent factors for the decrease in eGFRcr or Ccr during the 2-year denosumab therapy. Decline in creatinine-based renal function could be reflected by increased muscle mass during the ongoing recovery from fracture. Conclusions Renal function was preserved in all patients, including those in the switch group during denosumab therapy. Creatinine-based renal function should be cautiously interpreted during denosumab therapy in patients with recent fractures.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. METHODS: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. RESULTS: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. CONCLUSION The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

BACKGROUND: Through the analysis of clinical data, we attempted to investigate the etiology and determine the risk of severe iatrogenic lingual nerve injuries in the removal of the mandibular third molar. METHODS: A retrospective chart review was performed for patients who had undergone microsurgical repair of lingual nerve injuries. The following data were collected and analyzed: patient sex, age, nerve injury side, type of impaction (Winter's classification, Pell and Gregory's classification). Ratios for the respective lingual nerve injury group data were compared with the ratios of the respective data for the control group, which consisted of data collected from the literature. The data for the control group included previous patients that encountered various complications during the removal of the mandibular third molar. RESULTS: The lingual nerve injury group consisted of 24 males and 58 females. The rate of female patients with iatrogenic lingual nerve injuries was significantly higher than the control groups. Ages ranged from 15 to 67 years, with a mean age of 36.5 years old. Lingual nerve injury was significantly higher in the patient versus the control groups in age. The lingual nerve injury was on the right side in 46 and on the left side in 36 patients. There was no significant difference for the injury side. The distoangular and horizontal ratios were the highest in our lingual nerve injury group. The distoangular impaction rate in our lingual nerve injury group was significantly higher than the rate for the control groups. CONCLUSION Distoangular impaction of the mandibular third molar in female patients in their 30s, 40s, and 50s may be a higher risk factor of severe lingual nerve injury in the removal of mandibular third molars.