Induction of Paraptotic Cell Death in Cancer Cells by Triptycene-Peptide Hybrids and the Revised Mechanism of Paraptosis II.

In previous work, we reported on iridium(III) (Ir(III)) complex-peptide hybrids as amphiphilic conjugates (IPH-ACs) and triptycene-peptide hybrids as amphiphilic conjugates (TPH-ACs) and found that these hybrid compounds containing three cationic KK(K)GG peptide units through C6-C8 alkyl linkers induce paraptosis II, which is one of the nonapoptotic programmed cell death (PCD) types in Jurkat cells and different from previously reported paraptosis. The details of that study revealed that the paraptosis II induced by IPH-ACs (and TPH-ACs) proceeds via a membrane fusion or tethering of the endoplasmic reticulum (ER) and mitochondria, and Ca2+ transfer from the ER to mitochondria, which results in a loss of mitochondrial membrane potential (ΔΨm) in Jurkat cells. However, the detailed mechanistic studies of paraptosis II have been conducted only in Jurkat cells. In the present work, we decided to conduct mechanistic studies of paraptosis II in HeLa-S3 and A549 cells as well as in Jurkat cells to study the general mechanism of paraptosis II. Simultaneously, we designed and synthesized new TPH-ACs functionalized with peptides that contain cyclohexylalanine, which had been reported to enhance the localization of peptides to mitochondria. We found that TPH-ACs containing cyclohexylalanine promote paraptosis II processes in Jurkat, HeLa-S3 and A549 cells. The results of the experiments using fluorescence Ca2+ probes in mitochondria and cytosol, fluorescence staining agents of mitochondria and the ER, and inhibitors of paraptosis II suggest that TPH-ACs induce Ca2+ increase in mitochondria and the membrane fusion between the ER and mitochondria almost simultaneously, suggesting that our previous hypothesis on the mechanism of paraptosis II should be revised.

Comparison of masticatory performance and oral hygiene status using cream-type denture adhesives and home liners: A cross-sectional study using propensity-score matching.

BACKGROUND: Differences in the effects of cream-type denture adhesives and home liners remain unclear. OBJECTIVE: This cross-sectional study aimed to clarify the differences in the oral-hygiene status and masticatory performance between participants using cream-type denture adhesives and those using home liners. METHODS: Masticatory performance with and without cream-type denture adhesives and home liners was evaluated using colour-changeable chewing gum. Oral hygiene was assessed using the tongue coating index (TCI). Propensity-score matching was performed using oral moisture, presence of palatal or mandibular protuberances, type of residual ridge, denture type (complete or partial denture), and denture retention as background factors. Wilcoxon signed-rank test was used to examine the differences in masticatory performance with and without cream-type denture adhesives and home liners and differences in masticatory performance and TCI between the cream-type denture adhesive and home-liner groups. RESULTS: This study included 38 and 40 cream-type adhesive and home-liner users, respectively, and 17 pairs were obtained after propensity-score matching. The Wilcoxon signed-rank tests showed that masticatory performance was significantly different with and without the use of home liners, and higher values were obtained with the use of home-liners. However, the cream-type denture adhesive and home-liner groups showed no significant differences in terms of the change in masticatory performance with the use of them. Furthermore, Wilcoxon signed-rank tests showed that TCI values were significantly high in the cream-type adhesive group. CONCLUSION: The findings in this study suggest that home liners improve masticatory performance and that participants regularly using cream-type denture adhesives have poorer oral hygiene.

Comorbid thrombosis as an adverse prognostic factor in patients with ovarian clear cell carcinoma regardless of staging.

OBJECTIVE: Patients with ovarian clear cell carcinoma (OCCC) often present with thrombosis. While cancer patients with concomitant thrombosis were generally reported to have worse prognoses than those without, the association between thrombosis and prognosis has not been elucidated in OCCC. This study aimed to determine how the co-occurrence of thrombosis affects OCCC prognoses. METHODS: We retrospectively examined 115 patients with OCCC who were diagnosed and treated at the University of Tokyo Hospital between 2009 and 2019. RESULTS: Of 115 patients with OCCC, thrombosis was present in 12.5% of 80 patients and in 42.8% of 35 patients who had OCCC stage I/II and stage III/IV, respectively. In stage I/II, the 5-year progression-free survival was 20.6% and 91.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 50.0% and 94.1%. Therefore, the outcomes were significantly poorer among patients with thrombosis (p < 0.0001 and p < 0.0001, respectively). In stage III/IV, the 5-year progression-free survival was 26.7% and 52.8% among patients with thrombosis and among those without, respectively, while the corresponding 5-year overall survival rates were 32.0% and 62.2%. Similarly, the outcomes were significantly poorer among patients with thrombosis (p = 0.0139 and p = 0.369, respectively). CONCLUSION: We determined that thrombosis is more likely to develop in advanced OCCC stages than in early stages, and its co-occurrence is associated with a poor prognosis, regardless of disease stage.

Time spent away from bed is associated with oral hygiene and oral function: A cross-sectional and multi-institutional study.

BACKGROUND: Spending time away from bed is important in older adults. Not doing so can lead to functional decline rapidly. OBJECTIVE: To investigate the association between oral function and time spent away from bed in older adults living in nursing homes. METHODS: We enrolled 748 adults aged ≥65 years across eight nursing homes between April 2022 and March 2023. 'Problems with oral hygiene' and 'problems with oral function' were the dependent variables in the multiple regression analyses to determine their association with time spent away from bed. RESULTS: We selected 304 participants (76 men; mean age, 86.3 ± 7.5 years) and divided them into three groups: group S (< 4 h), group M (4 to < 6 h) and group L (≥ 6 h), with 28, 23 and 253 participants, respectively. Comparison of the characteristics between the groups demonstrated significant differences in the Barthel index (p < .001), time spent away from bed (p < .001), history of aspiration pneumonia (p < .001), confirmation of meals and food forms (p = .010), problems with oral hygiene (p = .014), and problems with oral function (p = .002). Based on multiple regression analyses, 'problems with oral hygiene' (p < .001) and 'problems with oral function' (p < .001) were significantly associated with time spent away from bed. CONCLUSIONS: The time spent away from bed was significantly associated with both oral hygiene and function in older adults, suggesting the importance of extending the time that older adults spend away from bed.

Effect of oral intake initiation-establishment interval on hospital stay after oral cancer surgery.

OBJECTIVES: To clarify the effect of the period between initiation of oral intake (IOI) and establishment of oral intake (EOI) on length of hospital stay. METHODS: This retrospective study included postoperative oral cancer patients. The number of days from surgery to IOI and EOI and between IOI and EOI were recorded. We performed intergroup comparisons and Cox regression analysis using the number of days until discharge, representing hospital stay length as the dependent variable. RESULTS: The median number of days between IOI and EOI was 3 days for eligible patients and 4.5 and 1.5 for older and younger patients, respectively. The median number of days from surgery to IOI was 15 days. There was a significant correlation between the period between IOI and EOI and the length of hospital stay (r = 0.40, p < 0.01). The period between IOI and EOI was a significant independent variable for the length of hospital stay (HR [95% confidence interval] = 0.45 [0.28-0.72]). CONCLUSIONS: Shortening the IOI to EOI intervals was identified as an independently associated factor for shortening hospital stay, even in older postoperative patients with dysphagia who struggled with early oral intake initiation. Professional, step-by-step dysphagia rehabilitation tailored to the patient's condition yields beneficial outcomes.

Accuracy of newly developed color determination application for masticatory performance: Evaluating color-changeable chewing gum.

PURPOSE: Color-changeable chewing gums are used to evaluate masticatory performance, as measured by a colorimeter or visually based on a color scale. Although anyone can use a color scale, the evaluation accuracy depends on the evaluator. We develop an application that can determine the degree of color change in chewing gum using smartphone images, making color evaluation accurate and easy to measure. METHODS: For the application, 60 chewed gum samples were prepared. Two shots were captured using two smartphone models. To create the application algorithm, a formula was developed to approximately map the color value from the smartphone images to the true value using a colorimeter. A basic validation was performed on 60 new samples covering a range of colors, followed by a field validation on 100 healthy dentate participants aged 20-39 years. RESULTS: The intraclass correlation coefficient for two repeated shots had a high value ≥ 0.97 in the basic and field validations, confirming reliability. No significant differences were observed in the paired t-test and Wilcoxon signed-rank test, and a significant and strong correlation (correlation coefficient ≥ 0.92) was observed between the evaluation values using the colorimeter and the basic and field validations. Bland-Altman plots further confirmed the validity of the application. CONCLUSIONS: A software application was developed to enable easy, quick, and accurate determination of the masticatory performance of a chewing gum from images taken using a smartphone with highly reliable and validated results.

Lack of Physician-Dentist Collaboration in Aspiration Pneumonia Prevention.

This opinion paper addresses the challenges and future directions for preventing aspiration pneumonia in Japan's rapidly aging population. It highlights the increasing proportion of elderly individuals and the associated rise in health issues like decreased swallowing function, a risk factor for aspiration pneumonia. The paper emphasizes the effectiveness of dentist-provided oral care in preventing this condition but notes the lack of collaboration between dentists and physicians in Japan's clinical practice. Key challenges identified include the scarcity of full-time hospital dentists, insufficient communication between physicians and dentists, limited patient understanding and motivation regarding oral care, and a lack of training in geriatric dentistry. The paper advocates for enhanced awareness among healthcare professionals and patients, increased hospital dentists, and improved collaboration mechanisms, particularly in light of recent positive changes in insurance reimbursement policies for elderly oral care.

Physical, oral, and swallowing functions of three patients with type a xeroderma pigmentosum: a report of three cases.

BACKGROUND: Xeroderma pigmentosum (XP) is an extremely rare and severe form of photosensitivity. It is classified into types A-G or V according to the gene responsible for the disease. The progression and severity of symptoms vary depending on the type. Although dysphagia caused by decreased swallowing function and dental malposition due to stenosis of the dentition in the facial and oral regions is common, it has not been reported in detail. We report three cases of type A XP, in which central and peripheral neurological symptoms appeared early on and progressed rapidly. We describe the oral function of these patients, focusing on the swallowing function and dentition malposition. CASE PRESENTATION: Two males (27 and 25 years old) and one female (28 years old) presented with diverse neurological symptoms. We focused on the relationship between the changes in swallowing and oral functions and conditions due to decline in physical function. Some effects were observed by addressing the decline in swallowing and oral functions. In particular, a dental approach to manage the narrowing of the dentition, which was observed in all three patients, improved the swallowing and oral functions and maintained the current status of these functions. CONCLUSIONS: In type A XP, early decline in oral and swallowing functions is caused by the early decline in physical function, and it is necessary to monitor the condition at an early stage.

Development and evaluation of a new intraoral voice assist device called the voice retriever.

Objective: Patients lose their voice after laryngectomy for laryngeal cancer or aspiration prevention surgery for severe dysphagia. To assist such patients, we developed and verified the utility of a novel vocalization method using a device termed the voice retriever (VR), in which the sound source is placed in the mouth. Methods: We investigated the effectiveness of the VR in patients. The VR consists of a mouthpiece with a built-in speaker and a dedicated application that serves as the sound source. We compared the speech intelligibility and naturalness in normal participants using VR and an electrolarynx (EL) for the first time as well as the voice-related quality of life (V-RQOL) in patients with dysphonia before and after using the VR. Results: The VR produced significantly higher 100-syllable test scores as well as fluency, amount of additional noise, intonation, intelligibility and overall long reading test ratings in the first-time VR and EL users. Furthermore, the VR use significantly improved the V-RQOL of participants with dysphonia. Conclusion: Compared to EL, VR allows more effective speech improvement in participants without experience using an alternative vocalization method and improves the V-RQOL in patients with dysphonia. Level of Evidence: Step 4.

Effect of poor oral health status at hospital admission on in-hospital outcomes of older patients with aspiration pneumonia.

PURPOSE: To investigate the effects of oral health status at admission on in-hospital outcomes and how it varies during hospitalization in older patients with aspiration pneumonia. METHODS: This prospective cohort study involved patients aged ≥ 65 years who were admitted to an acute care hospital with a diagnosis of aspiration pneumonia. The patients' basic health information, length of hospital stay (LOS), and oral health assessment tool (OHAT), functional oral intake scale (FOIS), pneumonia severity index, and clinical frailty scale scores were recorded. Patients were divided into two groups based on their median OHAT scores, and intergroup changes were analyzed as a function of time. The relationship between the LOS, FOIS score upon discharge, and OHAT scores at admission was examined using multiple regression analysis. RESULTS: Of the 89 participants (52 were men, with a mean age of 84.8 ± 7.9 years), 75 were discharged. The patients' oral health was measured weekly for 3 weeks after the initial assessment via the OHAT, wherein the median score was 7, with a significant between-group difference. Moreover, OHAT scores improved within both groups throughout their stay. OHAT scores at admission were independently associated with the LOS (B = 5.51, P = 0.009). CONCLUSION: Poor oral health status at admission was associated with longer hospital stays. Both the high- and low-OHAT groups showed OHAT score improvements. Oral health status is critical in preventing the onset of and treating aspiration pneumonia.

Characteristic hysteroscopy appearance considerations for detecting uterine endometrial malignancies.

AIM: The effectiveness of hysteroscopy in diagnosing endometrial lesions has been demonstrated, showing high diagnostic accuracy for malignant endometrial lesions. Although the characteristic appearances of atypical and malignant endometria have been reported, they are not definitive and sometimes complicated. This study aimed to identify a small number of characteristic features to detect endometrial abnormalities using a simple judgment system and analyze the diagnostic characteristics and their accuracy in endometrial malignancy diagnosis. METHODS: We performed a retrospective analysis of hysteroscopy video data of 250 patients, of which we selected for analysis based on pathology examination 152 cases with benign changes, 16 with atypical endometrium, and 18 with carcinoma in situ or endometrial cancer. Endometrial characteristics assessed included protrusion, desquamation, extended vessel, atypical vessel, and white/yellow lesion. RESULTS: Multivariable analysis revealed that desquamation (p = 0.001, odds ratio [OR] 5.28), atypical vessels (p < 0.001, OR 8.50), and white/yellow lesions (p = 0.011, OR 1.37) were significant predictors for endometrial malignancy. From their contribution status, scoring points of 4, 6, and 1 were settled according to the odds ratio proportions. When scores ≥5 (at least both desquamation and white/yellow lesions or only atypical vessels) were used to define endometrial malignancy, sensitivity and specificity were 100% and 92%, respectively. When detecting cancer, atypical, and benign cases, sensitivity and specificity were 88% and 90%, respectively. CONCLUSION: Our characteristics hysteroscopic findings showed a higher predictive ability in detecting endometrial malignancies. However, further examination with more cases would be needed to accurately diagnose endometrial malignancy by hysteroscopy.

Dental Care to Reduce Aspiration Pneumonia Recurrence: A Prospective Cohort Study.

BACKGROUND: Aspiration pneumonia has a high recurrence rate, and oral care by dentists has been found effective in preventing its onset; however, this has not been evaluated using prospective studies. Therefore, we conducted a prospective study to evaluate the effectiveness of professional oral care by dentists in reducing aspiration pneumonia recurrence in older adult patients. METHODS: In this prospective cohort study, we evaluated a dental oral care intervention, using a historical control group (control group). It was conducted at a single-centre regional core hospital in Japan that serves a large number of patients aged older than 80 years. Patients who were hospitalised for aspiration pneumonia were included in this study. During the study period (1 April 2021 to 31 March 2022), the clinical group received weekly professional cleaning by a dentist and the control group received standard oral care by a nurse as usual from 1 April 2020 to 31 March 2021. The dentist oral care group received weekly professional oral care from a dentist and was followed prospectively for 1 year. A Kaplan-Meier analysis was used to evaluate the timing of recurrent aspiration pneumonia or death. A Cox proportional hazards model was used to obtain a hazard ratio and determine the 95% confidence intervals. RESULTS: There were 91 participants in the clinical group and 94 in the control group. The mean age of participants was 85 years, and 75 (40.5%) were female. The recurrence rate was 27.5% in the clinical group and 44.7% in the control group (P = .005). Professional cleaning by a dentist reduced the risk of recurrence of aspiration pneumonia by approximately 50% (adjusted hazard ratio, 0.465; 95% confidence interval, 0.278-0.78). CONCLUSIONS: Professional cleaning by a dentist was associated with a lower rate of aspiration pneumonia recurrence than nurse-provided conventional oral care.

Impact of pureed and liquidised diets on health-related quality of life scores in older patients during postacute rehabilitation: A pilot study.

BACKGROUND: Consuming texture-modified diets was considered to negatively affect health-related quality of life (HR-QoL). However, the precise relationship between the levels of food texture consumed and HR-QoL remains uncertain. The present study aimed to determine the association between levels of food texture consumed and HR-QoL. METHODS: This cross-sectional study included 122 hospitalised patients aged ≥ 65 years (mean ± SD age 78.9 ± 7.9 years; 48.4% female) who required postacute rehabilitation. Consumed food texture levels were classified using the International Dysphagia Diet Standardization Initiative (IDDSI) framework 2.0. HR-QoL was evaluated using the five-level EuroQoL five-dimension (EQ-5D-5L). The association between food texture levels and HR-QoL was analysed using a multivariate linear regression model. RESULTS: The lower food texture levels consumed were associated with significantly lower EQ-5D-5L scores. Consumption of pureed (IDDSI Level 4) and liqudised (IDDSI Level 3) diets were associated with lower EQ-5D-5L scores among older patients undergoing postacute rehabilitation (regression coefficient -0.304; 95% confidence interval = -0.472 to -0.137 and regression coefficient, -0.444, 95% confidence interval = -0.676 to -0.213, respectivly). CONCLUSIONS: The findings suggest a link between the consumption of pureed and liquidised diets and lower HR-QoL scores in older hospitalised patients undergoing rehabilitation. To establish a clearer cause-and-effect relationship, future research should encompass multicentre and longitudinal studies, building upon the insights from the present study.

Kinematic analysis of chewing and swallowing function after cervical spine surgery.

PURPOSE: Although movement of the hyoid bone is different for masticatory swallowing and liquid swallowing in normal subjects, it has not been studied after cervical spine surgery. Therefore, we analyzed the swallowing dynamics of masticatory swallowing in anterior cervical spine disease surgery using foods that require chewing close to actual meals. METHODS: A day before and one week after the surgery, a videofluoroscopic swallow study (VFSS) was performed, and the distance of hyoid bone movement in the anterior and superior directions, amount of opening of the upper esophageal sphincter (UES), time of passage through the pharynx, number of swallows, and amount of pharyngeal residual were measured on the VFSS images during a masticatory swallow of corn flakes. The swallowing function was evaluated by DSS (dysphagia severity scale) and FOIS (functional oral intake scale). Imaging software was used for the measurements. RESULTS: Postoperative hyoid movement during masticatory swallowing was not significantly different for anterior movement but significantly limited in upward movement (p = 0.002); UES opening volume was significantly decreased (p < 0.001), and bolus residue was significantly worse (p < 0.001), compared to preoperative. The pharyngeal transit time was not significantly different; the number of swallows increased (p < 0.001), along with DSS (p < 0.001) and FOIS (p < 0.001), with significant differences before and after surgery, indicating worsened swallowing function. CONCLUSIONS: Swallowing function worsened in masticatory swallowing after surgery for cervical spine disease, mainly due to the restriction of upward movement of the hyoid bone and the resulting increase in pharyngeal residuals after swallowing.

Factors associated with the oral health status of patients with schizophrenia: A cross-sectional study.

BACKGROUND: Oral function deterioration attributed to ageing and medications is one of the main contributory factors of dysphagia. Therefore, oral health management is essential in older patients with schizophrenia. However, no previous studies have evaluated the oral function in patients with schizophrenia. OBJECTIVE: We surveyed patients with schizophrenia to identify factors associated with ageing-related variations in oral function. METHODS: This cross-sectional study included 34 male patients diagnosed with schizophrenia who were hospitalised at a psychiatric hospital between July and September 2021 and underwent a screening examination during dental care. The survey items included basic information, oral hygiene information, oral (oral diadochokinesis [ODK] and tongue pressure), physical function, and nutritional status. Thirty-six male community-dwelling older individuals were included as controls, and their outcomes were compared with those of patients with schizophrenia. RESULTS: Compared with healthy older adults, patients with schizophrenia demonstrated significantly lower teeth numbers, ODK, and calf circumference (CC) (p < .05). Multiple regression analysis revealed that ODK was associated with age and schizophrenia (p < .05). Conversely, tongue pressure was associated with CC (p < .05), suggesting different factors' association with the parameters indicating decreased oral function. CONCLUSIONS: Our study findings suggest that older patients with schizophrenia have decreased tongue pressure and generalised muscle mass, highlighting the need to manage oral function. Interventions for tongue pressure were more strongly associated with muscle mass and could be easier to manage than those with disease-dependent changes in ODK. TRIAL REGISTRATION: Retrospectively registered.

Association between Masticatory Performance, Nutritional Intake, and Frailty in Japanese Older Adults.

The older adult population in Japan is expected to increase. Therefore, long-term care and frailty prevention are important. However, the relationship between masticatory performance, nutritional intake, and frailty remains unclear. This cross-sectional study aimed to examine energy, protein, and vitamin D intake and its association with frailty and masticatory performance in older adults. Patients between January 2022 and January 2023 were recruited and divided into robust and frail groups. Masticatory performance, nutrition, frailty, and other data, such as age and sex, were evaluated through onsite measurements and a questionnaire. Logistic regression analysis was conducted with frailty as a dependent variable and masticatory performance as an independent variable, adjusting for age, sex, skeletal muscle mass, living alone, energy intake, protein-energy ratio, and vitamin D intake. No significant differences were observed between the groups regarding age or sex. The robust group showed significantly better results for protein-energy ratio, vitamin D intake, and subjective and objective masticatory performance than the frail group. Logistic regression analysis revealed a significant correlation between skeletal muscle mass, protein-energy ratio, and objective masticatory performance with frailty. Masticatory performance was associated with frailty, independent of the intake of nutrients such as energy, protein, and vitamin D.

Relationship between the jaw-closing force and dietary form in older adults without occlusal support requiring nursing care.

In clinical practice, we encounter cases wherein older adults lacking occlusal support consume foods requiring mastication and adequate swallowing function. This study investigated the relationship between jaw-closing force (JCF) and dietary form in older adults without occlusal support requiring nursing care. This prospective cross-sectional study included 123 older adults requiring nursing care who lost their molar occlusal support and consumed food orally without dentures. JCF was defined as the force required for crushing food with the edentulous ridges or with the tooth and edentulous ridge while closing the mouth. Participants were classified into four groups based on the International Dysphagia Diet Standardization Initiative framework for recommended dietary forms. Basic information was collected, and tongue pressure and JCF were measured. Differences in JCF were analyzed using one-way analysis of variance, while factors related to dietary form were evaluated using ordinal logistic regression analysis. Significant differences in JCF were observed among the four groups. Factors such as the Barthel Index, tongue pressure, and JCF were dietary form-related. Our findings suggest that older adults requiring nursing care tend to have higher JCF when consuming meals requiring mastication. Therefore, JCF could serve as an index for determining appropriate dietary forms in this population.

Tongue Strength of Older Adults Requiring Long-Term Care Varies throughout the Day.

Physical performance shows approximately 30% diurnal variation; however, diurnal variation in oral function remains unclear. This study aimed to determine the diurnal variation in oral and swallowing function in older adults requiring long-term care. The participants included 13 adults aged >60 years (3 men and 10 women, mean age: 77.2 ± 6.3 years, age range: 62-90 years) requiring long-term care. Tongue strength (TS) and oral mucosal moisture were measured as indices of oral and swallowing function, while hand grip strength was measured as an index of general muscle strength. The patients were asked to participate in a "test" after breakfast, lunch, and dinner on the same day. Multilevel linear regression analysis was used to examine diurnal differences in each item. Multilevel linear regression analysis with adjustment for age and sex revealed that TS was significantly higher at noon (p = 0.001) than in the morning. Therefore, caregivers who provide support during meals to older people requiring long-term care should consider the possibility of swallowing function differing according to the time of the day. In conclusion, it may be beneficial to establish a nutritional therapy that accounts for the diurnal variation in TS.