EphA-Mediated Regulation of Stomatin Expression in Prostate Cancer Cells.

BACKGROUND AND AIMS: Tumor growth and progression are affected by interactions between tumor cells and stromal cells within the tumor microenvironment. We previously showed that the expression of an integral membrane protein, called stomatin, was increased in cancer cells following their association with stromal cells. Additionally, stomatin impaired the Akt signaling pathway to suppress tumor growth. However, it remains unclear how stomatin expression is regulated. To explore this, we examined the cell surface molecules that can transduce the intercellular communication signals between cancer cells and stromal cells. RESULTS: Among these molecules, EphA3 and EphA7 receptors and their ligand ephrin-A5 were found to be expressed in prostate cancer cells, but not in prostate stromal cells. Cell-to-cell contact of prostate cancer cells through the EphA-ephrin-A interaction suppressed stomatin expression, while knockdown of EphA3/7 or ephrin-A5 increased stomatin expression. This increase contributed to an inhibition of prostate cancer cell proliferation. Intracellularly, the binding of ephrin-A to EphA attenuated extracellular signaling-regulated kinase (ERK) activation that promoted stomatin expression. Furthermore, ELK1 and ELK4, which are Ets family transcription factors phosphorylated by ERK, were involved in the induction of stomatin expression. We also found that higher Gleason score prostate cancer tissue samples had increased activation of EphA, while the stomatin expression and activated ERK and ELK levels were all low. In the mouse xenograft tumor samples generated by implantation of prostate cancer cells, EphA3 phosphorylation was attenuated and the ERK-ELK signaling and stomatin expression were enhanced in the area where stromal cells infiltrated the tumor. CONCLUSION: The EphA-mediated signaling suppresses the ERK-ELK pathway, leading to the reduction of stomatin expression that affects prostate cancer malignancy.

Effectiveness of Nutrition Support Team Intervention in Pediatric Patients with Cancer.

Malnutrition in children with cancer is associated with poor prognosis. This study aimed to determine whether nutritional support team (NST) interventions prevent adverse events and improve the nutritional status in pediatric patients admitted for cancer treatment. This was a historical cohort study of pediatric patients with acute lymphocytic leukemia, acute myeloid leukemia, neuroblastoma, or brain tumor who received chemotherapy or underwent hematopoietic stem cell transplantation. Patients admitted between June 2013 and October 2014 were classified into the intervention group. Those admitted between January 2011 and December 2012 were classified into the control group. We created a homogeneous probability model using the inverse probability of treatment weighting method, and compared outcomes. A total of 75 patients were included in the study (38 and 37 in the intervention and control groups, respectively). The intervention group had significantly fewer incidents of nothing by mouth (nil per os [NPO]) (p=0.037) and days of NPO (p=0.046) than the control group. There was no significant difference between the intervention and control groups regarding the change in body mass index z-score between admission and discharge (p=0.376). NST interventions for children with cancer were associated with a reduction in the number of NPO occurrences and NPO days. These findings suggest that NST interventions contribute to continued oral intake.

Effects of sarcopenia on changes in prevalence of patients with depressive mood during hospitalization in geriatric rehabilitation.

Background: The effect of sarcopenia on depressive mood during geriatric rehabilitation remains unclear. This study investigated the potential influence of sarcopenia on depressive mood among geriatric patients in a rehabilitation setting. Methods: This observational cohort study enrolled 204 patients aged ≥65 years (mean: 78.8±7.6 years, 45.1% women) admitted to a rehabilitation unit between April 2020 and July 2021. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment (AWGS2019) criteria, which include low handgrip strength and muscle mass. Depressive mood was defined as a 15-item Geriatric Depression Scale score of ≥6 points. We applied logistic regression models to examine the influence of sarcopenia on depressive mood at discharge. Results: We observed sarcopenia in 58.3% of patients. The logistic regression model showed that sarcopenia negatively influenced depressive mood at discharge (odds ratio, 5.460; 95% confidence interval, 2.344-13.415). Of the 68 patients without depressive mood at admission, those with sarcopenia (n=31) had a significantly higher incidence of depressive mood at discharge compared with patients without sarcopenia (n=37) (41.9% vs. 16.2%, p=0.037). Conclusion: Sarcopenia at admission negatively affected depressive mood at discharge from geriatric rehabilitation. Thus, early and routine assessment of sarcopenia is vital for patients undergoing geriatric rehabilitation.

Association between the incidence of functional disability and frequency of eating together among older adults living alone: a 6-year follow-up study from the Japan Gerontological Evaluation Study.

OBJECTIVE: This study aimed to determine whether the frequency of eating together is associated with the incidence of functional disability in older adults who live alone. METHODS: This 6-year observational prospective cohort study utilised self-reported questionnaires. Data were drawn from the participants of the Japan Gerontological Evaluation Study project between 2016 and 2022. The participants were independent older adults aged ≥65 years living alone in Japan. The primary outcome was the incidence of functional disability during the follow-up period, with the self-reported frequency of eating together serving as the explanatory variable. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models after adjusting for confounders associated with incident functional disability. RESULTS: Among the 7167 participants, the mean age at baseline was 75.3 ± 6.5 years and 69.2% were female. About, 12.8% of participants (n = 917) developed functional disabilities during the observation period. The incidence rates were 11.7% for 'every day', 11.3% for 'several times a week', 11.5% for 'several times a month', 12.7% for 'several times a year' and 19.0% for 'seldom'. The frequency of eating together 'seldom' was significantly associated with an increased incidence of functional disability (HR: 1.55, 95% CI: 1.10-2.18). CONCLUSION: Among older adults living alone, infrequent eating together ('seldom') was identified as a risk factor for developing functional disability.

Oral hypofunction and social aspects in older adults visiting frailty outpatient clinic.

BACKGROUND: Oral and social problems can exacerbate long-term care. Understanding the relationship between social aspects and oral hypofunction can help identify high-risk factors for long-term care. OBJECTIVE: This study aimed to investigate the social aspects of oral hypofunction among medical outpatients. METHODS: This retrospective cross-sectional study included patients who visited an outpatient clinic for frailty. The oral function was assessed using seven items: oral hygiene, occlusal force, masticatory function, tongue-lip motor function, tongue pressure, oral dryness and swallowing function. Participants with three or more functional declines were classified as having 'oral hypofunction'. Social aspects were assessed using 21 items in four categories: general resources, basic social needs, social resources and social behaviours/activities. We analysed the relationship between oral hypofunction and each social aspect. RESULTS: A total of 316 participants (age 78.5 ± 6.4 years) were included, and 128 (41%) had oral hypofunction. Participants with oral hypofunction were significantly more likely to have limited education, require long-term care, not use transportation, depend on others for shopping, not participate in events, lack association membership and not engage in charity or volunteer work. After logistic regression analysis, 'long-term care' and 'no association membership' remained significantly associated with oral hypofunction (odds ratios 2.3, 2.3; 95% CI 1.1-5.0, 1.1-4.7, respectively). CONCLUSION: Participants with oral hypofunction faced challenges in 'general resources' and 'social behaviour/activities', which were linked to oral function issues. Future longitudinal studies are necessary to further investigate this relationship.

Association Between Malnutrition and Food Texture Levels in Integrated Facilities for Medical and Long-Term Care.

OBJECTIVES:  This study aims to investigate the association between malnutrition using the global consensus criteria and food texture levels in residents of Integrated Facilities for Medical and Long-Term Care (IFMLCs), which are new long-term care insurance facilities in Japan. METHODS: This single-center study had a retrospective cross-sectional design. The study was conducted from November 1 to 30, 2021, and the study participants were residents admitted to an IFMLC during the study period. Malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. Food texture levels consumed by patients at admission were categorized based on the International Dysphagia Diet Standardization Initiative (IDDSI) framework. Multivariate logistic regression models were used to determine the association between the food texture levels consumed and malnutrition. RESULTS: A total of 98 older residents were analyzed in this study. The median age of the participants was 88 years, and 68 (69%) female participants were included. The IDDSI framework levels were 24% in levels 7 and 6 and 26% in levels 5 and 4. A significant difference in the prevalence of low BMI, reduced muscle mass, and reduced food intake or assimilation was noted between IDDSI framework levels 4 and 7. Multivariate logistic regression analysis was performed for malnutrition, adjusting simultaneously for potential confounders. IDDSI level 4 (odds ratio, 5.074; 95% confidence interval, 1.059-28.092; p=0.042) consumption was independently associated with malnutrition. CONCLUSIONS: The consumption of lower food texture levels categorized using the IDDSI framework was associated with a higher malnutrition prevalence in IFMLC residents.

Optimization of method for cross-section hydrogels preparation using high-pressure freezing.

High-pressure water freeze fracturing is a method for preparing water-containing samples such as hydrogels for scanning electron microscopy (SEM), in which a sample is placed in a divisible pressure vessel, filled with water, sealed, frozen with liquid nitrogen and then vacuum dried after the vessel is divided. The pressure (∼200 MPa) generated by the phase transition from water to ice is expected to inhibit ice crystal formation that causes large deformation of microstructure in the sample. To maximize the useable sample size, where SEM observation is not affected by ice crystal growth, preparation conditions including the size of pressure vessel were examined in this work. Using pressure vessels 8.0 mm, 5.5 mm and 4.5 mm in diameter, agarose gel, gelatin gel, wheat starch hydrogel, wheat flour noodle and cellulose hydrogel were used to prepare SEM samples. With agarose gel, an area of 3.6 mm in diameter in the 5.5 mm vessel was achieved as the maximum size of the area observable without ice crystal growth. The observable size of other samples was comparable, except for gelatin gel. As a result, observation of the three-dimensional network structure of hydrogels could be performed over a wider range than with the conventional method without shredding or chemical treatment of the samples. Additionally, usability of agarose gel for sample support matrix in high-pressure water freeze fracturing was demonstrated.

Cutoff value of the geniohyoid muscle mass to identify sarcopenic dysphagia by ultrasonography.

PURPOSE: Determining the strength and area of the swallowing muscles is important in patients with sarcopenic dysphagia. Although the normative data on the strength of the swallowing muscles have been reported, those of the area of the geniohyoid muscle are poorly investigated. We investigated the cross-sectional area of the geniohyoid muscle in Japanese subjects without dysphagia using ultrasonography to determine the normative and cut-off values. METHODS: 142 subjects without dysphagia were included. The older group (age ≥ 65 years) included 36 (women 27/men 9) subjects, and the younger group (age ≤ 39 years) included 106 (women 54/men 52) subjects. The cross-sectional area of the geniohyoid muscle was measured by ultrasound. The mean of the younger group-2 standard deviation (SD) was calculated and used as a cut-off value for low swallowing muscle mass. RESULTS: The mean (SD) of the area of the geniohyoid muscle of each group was as follows: older women group 167.2 (32.6) mm2, older men group 193.2 (49.5) mm2, younger women group 247.3 (37.4) mm2, younger men group 313.1 (59.2) mm2. The mean 2SD of the geniohyoid muscle area in the younger women group was 172.5 mm2 and in the younger men group 194.7 mm2. CONCLUSION: We found that the cut-off value of the ultrasonographic cross-sectional area of the geniohyoid muscle was 172.5 mm2 for women and 194.7 mm2 for men. These values could be used as cut-off values for the mass of the geniohyoid muscle to identify patients with sarcopenic dysphagia.

Association between oral frailty and sarcopenia among frailty clinic outpatients: A cross-sectional study.

OBJECTIVES: In this study, we aimed to investigate the prevalence of oral frailty and explore its relationship with oral function and sarcopenia among older outpatients. MATERIALS AND METHODS: In this cross-sectional study, we retrospectively included older patients who visited a frailty outpatient clinic. We assessed total oral frailty employing, among other measures, oral diadochokinesis (/ta/ sound) for tongue-lip movement and tongue pressure. Patients who did not meet the cut-off values for three or more of these were classified as having oral frailty. Sarcopenia was assessed according to Asian Working Group for Sarcopenia 2019 criteria and analyzed for the relationship with oral function. RESULTS: The mean ± standard deviation age of the 111 patients was 77.2 ± 5.7 y; 63 were women (57%). Fifteen patients (14%) had either sarcopenia or dynapenia. The overall prevalence of oral frailty was 38%, with no significant difference in its prevalence between the sarcopenia/dynapenia group (44%) and the robust (no sarcopenia/dynapenia) group (35%). The following oral function assessments significantly differed between the sarcopenia/dynapenia group and the robust group: median (interquartile range) total oral frailty score, 2 (2-4) and 2 (1-3) (P = 0.019); tongue-lip motor function, 5.4 ± 1.2 and 5.9 ± 1.2 times/s (P = 0.049); and tongue pressure, 27.3 ± 8.5 kPa and 31.7 ± 8.0 kPa (P = 0.009). CONCLUSIONS: Approximately 40% of patients exhibited a decline in oral function regardless of the presence of sarcopenia. Sarcopenia and dynapenia may particularly affect tongue function. Although assessing patients for sarcopenia is crucial, separate evaluations of oral function should also be considered.

Predicting Mortality Risks Using Body Mass Index and Weight Loss at Admission in Patients with Heart Failure.

BACKGROUND: The association of the combination of body mass index (BMI) and weight change at admission with prognoses in patients with heart failure (HF) is unclear. Therefore, we investigated whether BMI and weight changes at admission affect mortality in patients with HF. METHODS: This retrospective cohort study lasted 99 months, starting in April 2014, and included 4,862 patients with HF from a Japanese real-world database. Cubic and thin-plate smoothing spline analyses were performed to investigate the association of BMI and weight changes with mortality. The percentage weight change was calculated every 6 months. The study outcome was the presence or absence of death. RESULTS: The patients' mean age was 81.5±9.6 years, and 1,239 (25.5%) patients died. Cubic spline analysis revealed a negative correlation of BMI with mortality hazard ratio (HR) (BMI of 18.5 kg/m2 and 25 kg/m2; HR=1.3 [1.2-1.4] and 0.8 [0.7-0.9], respectively). Cubic spline analysis of weight change showed that weight loss tended to increase the mortality HR (each 6% decrease in weight change rate was associated with a 1.1 times higher mortality risk (95% CI [1.0-1.2]) Thin-plate smoothing spline analysis showed that the odds ratio (OR) negatively correlated with BMI (1-year mortality: BMI of 18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.5, 1.0, and 0.7, respectively; 2-year mortality: BMI=18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.4, 0.9, and 0.7, respectively). CONCLUSION: A low BMI in patients with HF was associated with a higher risk of mortality. Weight loss in patients, regardless of BMI, was associated with a higher OR for mortality.

Hospitalization-associated disability prediction using Hospital Frailty Risk Score in older patients undergoing pancreatectomy.

PURPOSE: Frailty and hospitalization-associated disabilities (HAD) are geriatric conditions that should be managed in older patients undergoing pancreatectomy. The Hospital Frailty Risk Score (HFRS) can evaluate frailty based on medical records and could predict postoperative activities of daily living (ADL) decline. This study aimed to investigate whether HFRS affects the postoperative incidence of HAD in older patients who underwent pancreatectomy. METHODS: This retrospective, observational study used data from a nationwide hospital-based database. We included consecutive patients aged ≥ 65 years who were diagnosed with pancreatic cancer (International Statistical Classification of Diseases, 10th revision code C25) and underwent curative pancreatectomy between April 2014 and August 2020. We evaluated preoperative frailty using HFRS. The primary outcome was HAD following pancreatectomy. Logistic regression analysis was performed for analyzing the impact of frailty on HAD following pancreatectomy. RESULTS: We included 671 patients for the analysis (mean age 74.3 ± 5.6, male 54.8%). The prevalence of intermediate and high risk of frailty with HFRS ≥ 5 was 2.7%. The incidence of HAD was significantly higher in the intermediate- and high-risk groups compared to that in the low-risk group (33.3% vs. 8.4%, p < 0.001). Logistic regression analysis demonstrated that intermediate and high risks of frailty increased the likelihood of HAD (odds ratio, 3.55; 95% confidence interval: 1.12-11.2). CONCLUSIONS: The risk of frailty evaluated using the HFRS increased the likelihood of developing HAD in older patients undergoing pancreatectomy. Future research on effective perioperative interventions for preventing postoperative HAD and enhancing postoperative ADL recovery is warranted.

Polypharmacy, Potentially Inappropriate Medications, and Dysphagia in Older Inpatients: A Multi-Center Cohort Study.

BACKGROUND: Although the relationship between medication status, symptomatology, and outcomes has been evaluated, data on the prevalence of polypharmacy and potentially inappropriate medications (PIMs) and the association of polypharmacy and PIMs with swallowing function during follow-up are limited among hospitalized patients aged ≥65 years with dysphagia. METHODS: In this 19-center cohort study, we registered 467 inpatients aged ≥65 years and evaluated those with the Food Intake LEVEL Scale (FILS) scores ≤8 between November 2019 and March 2021. Polypharmacy was defined as prescribing ≥5 medications and PIMs were identified based on the 2023 Updated Beers Criteria. We applied a generalized linear regression model to examine the association of polypharmacy and PIMs with FILS score at discharge. RESULTS: We analyzed 399 participants (median age, 83.0 years; males, 49.8%). The median follow-up was 51.0 days (interquartile range, 22.0-84.0 days). Polypharmacy and PIMs were present in 67.7% of and 56.1% of patients, respectively. After adjusting for covariates, neither polypharmacy (ß = 0.05; 95% confidence interval [CI], -0.04-0.13, p=0.30) nor non-steroidal anti-inflammatory medications (ß = 0.09; 95% CI, -0.02-0.19; p=0.10) were significantly associated with FILS score at discharge. CONCLUSION: The results of this study indicated a high proportion of polypharmacy and PIMs among inpatients aged ≥65 years with dysphagia. Although these prescribed conditions were not significantly associated with swallowing function at discharge, our findings suggest the importance of regularly reviewing medications to ensure the appropriateness of prescriptions when managing older inpatients.

Establishment of a novel mouse model of renal artery coiling-based chronic hypoperfusion-related kidney injury.

Renal artery stenosis-induced chronic renal ischemia is an important cause of renal dysfunction, especially in older adults, and its incidence is currently increasing. To elucidate the mechanisms underlying chronic renal hypoperfusion-induced kidney damage, we developed a novel mouse model of renal artery coiling-based chronic hypoperfusion-related kidney injury. This model exhibits decreased renal blood flow and function, atrophy, and parenchymal injury in the coiled kidney, along with compensatory hypertrophy in the non-coiled kidney, without chronic hypertension. The availability of this mouse model, which can develop renal ischemia without genetic modification, will enhance kidney disease research by serving as a new tool to investigate the effects of acquired factors (e.g., obesity and aging) and genetic factors on renal artery stenosis-related renal parenchymal damage.

Null mutation of exocyst complex component 3-like does not affect vascular development in mice.

Exocyst is an octameric protein complex implicated in exocytosis. The exocyst complex is highly conserved among mammalian species, but the physiological function of each subunit in exocyst remains unclear. Previously, we identified exocyst complex component 3-like (Exoc3l) as a gene abundantly expressed in embryonic endothelial cells and implicated in the process of angiogenesis in human umbilical cord endothelial cells. Here, to reveal the physiological roles of Exoc3l during development, we generated Exoc3l knockout (KO) mice by genome editing with CRISPR/Cas9. Exoc3l KO mice were viable and showed no significant phenotype in embryonic angiogenesis or postnatal retinal angiogenesis. Exoc3l KO mice also showed no significant alteration in cholesterol homeostasis or insulin secretion, although several reports suggest an association of Exoc3l with these processes. Despite the implied roles, Exoc3l KO mice exhibited no apparent phenotype in vascular development, cholesterol homeostasis, or insulin secretion.

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.