Inhibition of glutamine metabolism increases sensitivity to plasma-activated medium-induced cytotoxicity.

Non-thermal atmospheric pressure plasma (NTP), an ionized gas containing electrons, ions, radicals, and photons, has various biological effects, including wound healing and anticancer effects. Plasma-activated medium (PAM), which is prepared by irradiating medium with NTP, preferentially kills cancer cells. Large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS) included in PAM are closely related to its anticancer effects. The precise mechanism of PAM-induced cytotoxicity is not fully understood; however, PAM exposure has been reported to reduce cellular energy metabolism. Glutamine (Gln) is an important amino acid as an energy source in cancer cells. Gln is converted to glutamate by glutaminase (GLS), and is utilized to synthesize ATP and glutathione (GSH). Expression levels of GLS have been shown to be higher in certain types of cancers. In this study, we examined the effects of GLS inhibition on PAM cytotoxicity using breast cancer MDA-MB-231 cells. Pretreatment with BPTES, a glutaminase 1 (GLS1) inhibitor, dose-dependently enhanced PAM-induced cell death. PAM-induced ROS production and γ-H2AX formation, a DNA damage marker, were increased in cells pretreated with BPTES compared with PAM alone. BPTES pretreatment enhanced a PAM-induced decrease in intracellular GSH, indicating the possibility that BPTES reduces the antioxidant capacity of MDA-MB-231 cells. In addition, BPTES pretreatment enhanced PAM-induced loss of the mitochondrial membrane potential and reduction of ATP production. Moreover, GLS1 knockdown promoted PAM-induced cell death. Taken together, the combination of GLS1 inhibitors such as BPTES is considered to be useful for enhancing the cytotoxic effects of PAM against cancer cells.

Relationship Between Immunophenotypes, Genetic Profiles, and Clinicopathologic Characteristics in Small Bowel Adenocarcinoma.

Small bowel adenocarcinoma (SBA) is rare, and scant data exist regarding its molecular and clinicopathologic characteristics. This study aimed to clarify the correlation between immunophenotypes, DNA mismatch repair status, genomic profiling, and clinicopathologic characteristics in patients with SBA. We examined 68 surgical resections from patients with primary SBA for immunohistochemical analyses of CK7, CK20, CD10, CDX2, MUC1, MUC2, MUC4, MUC5AC, and MUC6 expression as well as mismatch repair status. Genomic profiling was performed on 30 cases using targeted next-generation sequencing. Tumor mucin phenotypes were classified as gastric, intestinal, gastrointestinal, or null based on MUC2, MUC5AC, MUC6, and CD10 immunostaining. The expression of these proteins was categorized into 3 classifications according to their relationship to: (1) tumor location: CK7/CK20, MUC4, and MUC6; (2) histologic type: mucinous adenocarcinoma was positive for MUC2 and negative for MUC6; and (3) TNM stage: CD10 was downregulated, whereas MUC1 was upregulated in advanced TNM stages. CDX2 was a specific marker for SBA generally expressed in the small intestine. MUC1 and MUC4 expression was significantly associated with worse prognosis. MUC2 expression correlated with better prognosis, except for mucinous adenocarcinoma. Although the difference was not statistically significant, gastric-type tumors were more frequently located in the duodenum and were absent in the ileum. APC and CTNNB1 mutations were not found in the gastric-type tumors. The SBA immunophenotype correlated with tumor location, biological behavior, and genomic alterations. Our results suggest that the molecular pathway involved in carcinogenesis of gastric-type SBA differs from that of intestinal-type SBA.

Effect of Exercise Therapy on Incident Admission in Patients with Type 2 Diabetes Mellitus Undergoing Inpatient Diabetes Self-management Education and Support Tokyo Metropolitan Toshima Hospital, Tokyo Metropolitan Hospital Organization, Japan.

BACKGROUND: Exercise therapy is the key to preventing admission of patients with type 2 diabetes mellitus (T2DM). However, a few studies have examined the effects of exercise therapy on patients with T2DM undergoing inpatient diabetes self-management education and support (IDSMES). OBJECTIVE: This study investigated whether exercise therapy influenced the incidence of admission after discharge in patients with T2DM undergoing IDSMES. METHODS: This retrospective cohort study included patients with T2DM who underwent IDSMES between June 2011 and May 2015. Overall, 258 patients were included in this study. The exercise therapy program was implemented in June 2013. Accordingly, patients diagnosed between June 2011 and May 2013 were categorized as the non-exercise therapy program group, while those diagnosed between June 2013 and May 2015 were categorized as the exercise therapy program group. Outcomes were incident diabetes-related and all-cause admissions within 1 year of discharge. Multiple logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the exercise therapy program's impact on the outcomes. RESULTS: Within 1 year of discharge, 27 (10.5%) patients underwent diabetes-related admissions and 62 (24.0%) underwent all-cause admissions. Multiple logistic regression analyses showed a significant association of the exercise therapy program with incident diabetes-related and allcause admissions [OR: 0.22 (95% CI: 0.08-0.59) and 0.44 (95% CI: 0.22-0.86), respectively]. CONCLUSION: Exercise therapy programs significantly lowered the incidences of diabetes-related and all-cause admissions. This indicates that implementing exercise therapy during hospitalization may be important for preventing admissions of patients with T2DM receiving IDSMES.

Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment.

BACKGROUND: Comprehensive genomic analysis has shown that small bowel adenocarcinoma (SBA) has different genomic profiles from gastric and colorectal cancers. Hence, it is essential to establish chemotherapeutic regimens based on SBA characteristics. The expression of programmed cell death-ligand 1 (PD-L1) and programmed cell death-ligand 2 (PD-L2) in SBA is not fully understood. Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes (TILs); therefore, the status of TILs in the tumor microenvironment (TME) may influence their efficacy. The ratio of FoxP3+ to CD8+ T cells has been reported to be useful in predicting the prognosis of digestive system cancers. AIM: To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues. METHODS: We performed immunohistochemical analysis for PD-L1, PD-L2, CD8, FoxP3, and DNA mismatch repair (MMR) proteins using formalin-fixed, paraffin-embedded tissues from 50 patients diagnosed with primary SBA. The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins, and finally evaluated using the combined positive score (CPS). We assessed CD8+ and FoxP3+ T cells in the intratumoral and tumor-surrounding stroma. Subsequently, we calculated and summed the ratio of FoxP3 to CD8+ T cell counts. Immune-related cell densities were graded as low or high. Immunohistochemical results were compared with clinicopathological factors and patient prognosis. The distribution of cancer-specific survival (CSS) was estimated using the Kaplan-Meier method, and the log-rank test was used to test for significant differences in CSS. A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS. RESULTS: PD-L1 expression was positive in 34% in tumor cells (T-PD-L1) and 54% in tumor-infiltrating immune cells (I-PD-L1) of the cases examined. T-PD-L2 was positive in 34% and I-PD-L2 was positive in 42% of the cases. PD-L1 CPS ≥ 10 and PD-L2 CPS ≥ 10 were observed in 50% and 56% of the cases, respectively. Deficient MMR (dMMR) was 14% of the cases. T-PD-L1, I-PD-L1 and PD-L1 CPS ≥ 10 were all significantly associated with dMMR (P = 0.037, P = 0.009, and P = 0.005, respectively). T-PD-L1, I-PD-L1, and PD-L1 CPS ≥ 10 were all associated with deeper depth of invasion (P = 0.001, P = 0.024, and P = 0.002, respectively). I-PD-L2 expression and PD-L2 CPS ≥ 10 were significantly higher in the differentiated histological type (P = 0.015 and P = 0.030, respectively). The I-PD-L1 and I-PD-L2 levels were significantly associated with better CSS (P = 0.037 and P = 0.015, respectively). CD8-high was significantly associated with less lymph node metastasis (P = 0.047), less distant metastasis (P = 0.024), less peritoneal dissemination (P = 0.034), and earlier TNM stage (P = 0.047). The CD8-high group had better prognosis than the CD8-low group (P = 0.018). FoxP3 expression was not associated with any clinicopathological factors or prognosis. We found that patients with PD-L2 CPS ≥ 10 tended to have worse prognosis in the FoxP3/CD8-low group (P = 0.088). CONCLUSION: The clinicopathological significance of PD-L1/2 expression may differ depending on the TME status. Immune checkpoint inhibitors may improve the prognosis of SBA patients with low FoxP3/CD8 ratio and PD-L2 expression.

Relationship between physical activity levels and changes in skeletal muscle characteristics in patients with stroke.

PURPOSE: This study aimed to investigate the relationship between physical activity (PA) levels and short-term changes in skeletal muscle characteristics in patients with subacute hemiparetic stroke. MATERIALS AND METHODS: This prospective observational study included 76 patients with stroke who received inpatient care in a convalescent rehabilitation ward. The PA level was measured as the duration of daily total PA (≥ 1.5 metabolic equivalents) using a triaxial accelerometer for 7 days after admission. The outcomes were changes in the quadriceps muscle quality and quantity on the affected and unaffected sides, as assessed by ultrasonography at admission and 1 month after admission. RESULTS: Multiple regression analysis indicated that the duration of total PA was significantly associated with a percentage change in quadriceps muscle quality (p = 0.011) and quantity (p = 0.012) on the affected side. However, no significant relationship was observed between the muscle quality and quantity on the unaffected side. CONCLUSIONS: The results revealed that PA was associated with changes in the quadriceps muscle quality and quantity on the affected side in patients with subacute hemiparetic stroke. These findings highlight the importance of promoting PA in stroke rehabilitation to improve muscle properties and functional outcomes.

Improving skeletal muscle quality and quantity is an important goal in post-stroke rehabilitation.We investigated physical activity and post-stroke changes in muscle properties.Physical activity is related to changes in muscle quantity and quality on the affected side.Promoting physical activity is essential for improving muscle quantity and quality on the affected side.

A U-shaped relationship between body mass index and functional recovery in older Japanese stroke survivors undergoing hospital rehabilitation.

OBJECTIVE: A relationship between body mass index and functional recovery in older survivors of stroke is unclear. Therefore, this study aimed to investigate the association of body mass index with post-stroke functional recovery in older Japanese stroke survivors undergoing hospital rehabilitation. METHODS: This was a multicenter retrospective observational study of 757 older survivors of stroke, from six convalescent rehabilitation hospitals in Japan. The participants were classified into seven categories according to body mass index at admission. The measurements included outcomes of the absolute gain in the motor subscale of the Functional Independence Measure. Poor functional recovery was defined as gain < 17 points. Multivariate logistic regression analysis was performed to examine the impact of these body mass index categories on poor functional recovery. RESULTS: The mean motor gains were highest in the 23.5-25.4 kg/m2 group (28.1 points), and lowest in the < 17.5 kg/m2 group (220.0 points). The results of the multivariate regression analyses (reference; 23.5-25.4 kg/m2 group) showed that the < 17.5 kg/m2 group (odds ratios 4.30; 95 % confidence intervals 2.09-8.87), the 17.5-19.4 kg/m2 group (1.99; 1.03-3.87), the 19.5-21.4 kg/m2 group (1.93; 1.05-3.54), and the ≥ 27.5 kg/m2 group (3.34; 1.33-8.42) were significantly associated with poor functional recovery, but not in the other groups. CONCLUSIONS: Older survivors of stroke with high-normal weight had the most favorable functional recovery among the seven groups. Meanwhile, both low and extremely high body mass indexes were associated with poor functional recovery.

Associations between caregiver burden and care receivers' sharing ratio of household tasks among spousal caregivers.

AIM: We assessed care receivers' sharing ratios of household tasks before they required care and investigated their relationship with caregiver burden. METHODS: A cross-sectional, online survey was completed by 272 spousal caregivers in Japan. Caregiver burden was assessed using the Zarit Burden Interview. Low and moderate-to-high caregiver burdens were defined as those with scores ≤40 and ≥41, respectively. Additionally, caregiver responses to, "How much did your partner contribute to household tasks before the onset of their condition that needed care?" were scored on a 10-point Likert scale ranging from 1 to 10. We defined answers that scored 1-4 as a low sharing ratio and those that scored 5-10 as a high sharing ratio of household tasks of care receivers before developing a condition that required care. RESULTS: Among the husband and wife caregivers, moderate-to-high caregiver burden in 33 (25.0%) and 48 (34.3%) caregivers, respectively. Multivariate logistic regression analysis showed that among the husband caregivers, the high sharing ratio of household tasks of their wives before developing a condition that required care was significantly associated with their caregiver burden (OR 4.55, 95% CI 1.20-17.27); however, no such association was observed among the wife caregivers (OR 0.85, 95% CI 0.37-2.29). CONCLUSIONS: Among husband, but not wife caregivers, the high sharing ratio of household tasks of their wives before they required care was significantly associated with their caregiver burden. Geriatr Gerontol Int 2023; 23: 616-621.

Combination of low muscle strength and malnutrition is associated with longer length of hospital stay among older patients with heart failure.

BACKGROUND: Muscle strength and nutritional status are associated with length of hospital stay (LOHS) in older patients with heart failure (HF). OBJECTIVES: The purpose of the study was to examine the association of the combination of muscle strength and nutritional status on LOHS in older patients with HF. METHODS: This retrospective cohort study included 414 older inpatients with HF (men, 57.2%; median age, 81 years; interquartile range, 75-86 years). Patients were categorized into four groups according to their muscle strength and nutritional status: group 1, high muscle strength and normal nutritional status; group 2, low muscle strength and normal nutritional status; group 3, high muscle strength and malnutrition; and group 4, low muscle strength and malnutrition. The outcome variable was the LOHS, and an LOHS of >16 days was defined as long LOHS. RESULTS: Multivariate logistic regression analysis adjusted for baseline characteristics (reference, group 1) showed that group 4 was associated with a more significant risk of long LOHS (odds ratio [OR], 3.54 [95% confidence interval, 1.85-6.78]). In the subgroup analysis, this relationship was maintained for the first admission HF group (OR, 4.65 [2.07-10.45]) but not for the HF readmission group (OR, 2.80 [0.72-10.90]). CONCLUSIONS: Our results suggest that the long LOHS for older patients with HF at first admission was associated with a combination of low muscle strength and malnutrition but not by either factor individually.

Quantum Annealing Boosts Prediction of Multimolecular Adsorption on Solid Surfaces Avoiding Combinatorial Explosion.

Quantum annealing has been used to predict molecular adsorption on solid surfaces. Evaluation of adsorption, which takes place in all solid surface reactions, is a crucially important subject for study in various fields. However, predicting the most stable coordination by theoretical calculations is challenging for multimolecular adsorption because there are numerous candidates. This report presents a novel method for quick adsorption coordination searches using the quantum annealing principle without combinatorial explosion. This method exhibited much faster search and more stable molecular arrangement findings than conventional methods did, particularly in a high coverage region. We were able to complete a configurational prediction of the adsorption of 16 molecules in 2286 s (including 2154 s for preparation, only required once), whereas previously it has taken 38 601 s. This approach accelerates the tuning of adsorption behavior, especially in composite materials and large-scale modeling, which possess more combinations of molecular configurations.

Comparison of Linked Color Imaging and White Light Imaging Colonoscopy for Detection of Colorectal Adenoma Requiring Endoscopic Treatment: A Single-Center Randomized Controlled Trial.

BACKGROUND: Linked color imaging (LCI) improves detection of colorectal neoplastic lesions during colonoscopy. However, polyps <5 mm in diameter often do not require resection, and the benefits of LCI are unclear for detection of colorectal polyps ≥5 mm that are indicated for endoscopic resection in clinical practice. This randomized controlled trial compared rates of detection of adenoma polyps, stratified by size, for LCI and white light imaging (WLI). METHODS: We compared ADR (5 mm-) and PDR (5 mm-), which were defined as the proportion of patients with at least one adenoma or polyp with a diameter of 5 mm or larger in the LCI and WLI groups. Moreover, we estimated ADR and PDR for diameters between 5 and 10 mm (ADR (5-9 mm), PDR (5-9 mm) ) and for diameters larger than 10 mm (ADR (10 mm-), PDR (10 mm-) ). RESULTS: Data from 594 patients (LCI, n=305; WLI, n=289) were analyzed. ADR (5 mm-) and PDR (5 mm-) were significantly higher in the LCI group than in the WLI group (ADR (5 mm-): P=0.016, PDR (5 mm-): P=0.020). In the assessment of adenoma and polyp size, ADR (5-9 mm) and PDR (5-9 mm) were significantly higher in the LCI group than in the WLI group, although no significant differences were seen in ADR (10 mm-) and PDR (10 mm-) between these groups. CONCLUSIONS: Polyps ≥5 mm, which are indicated for endoscopic treatment, were more easily visualized with LCI mode than with WLI mode. The improvement in detection rate was obvious for polyps <10 mm, which are easier to miss.

Impact of the quantity and quality of the skeletal muscle on survival among patients undergoing allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Poor skeletal muscle function is relatively high in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), leading to various negative health outcomes. This study aimed to investigate the relationship between the quantity and quality of skeletal muscle before transplantation and the short-to long-term survival after transplantation in patients undergoing allo-HSCT. METHODS: This retrospective cohort study included 156 patients undergoing allo-HSCT (men, 67.3 %; median age, 53 years; interquartile range, 42-61 years). The quantity and quality of the skeletal muscle were measured at the psoas major at the level of the third lumbar vertebrae using a computed tomography (CT) and were defined as psoas muscle index (PMI) and CT values (CTV), respectively. The outcome measure of this study was overall survival (OS) after allo-HSCT, and we examined the relationship between survival at three time points (6, 12, and 24 months) after transplantation, PMI, and CTV. RESULTS: PMI was significantly associated with survival at all time points in the crude model (P < 0.001), and a significant association was observed in the fully adjusted model (P < 0.01). CTV was significantly associated with survival at all time points in the crude model (P < 0.05), but not in the fully adjusted model (P > 0.05). CONCLUSIONS: We found that the quantity and quality of the skeletal muscle before transplantation were significantly associated with OS at 6, 12, and 24 months after transplantation, showing a particularly robust association with quantity.

Development and validation of ischemic heart disease and stroke prognostic models using large-scale real-world data from Japan.

BACKGROUND: Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly available, application of large datasets based on such real-world data can achieve prediction accuracy and support social implementation of cardiovascular disease risk prediction models in preventive and clinical practice. In this study, classical regression and machine learning methods were explored to develop ischemic heart disease (IHD) and stroke prognostic models using real-world data. METHODS: IQVIA Japan Claims Database was searched to include 691,160 individuals (predominantly corporate employees and their families working in secondary and tertiary industries) with at least one annual health check-up record during the identification period (April 2013-December 2018). The primary outcome of the study was the first recorded IHD or stroke event. Predictors were annual health check-up records at the index year-month, comprising demographic characteristics, laboratory tests, and questionnaire features. Four prediction models (Cox, Elnet-Cox, XGBoost, and Ensemble) were assessed in the present study to develop a cardiovascular disease risk prediction model for Japan. RESULTS: The analysis cohort consisted of 572,971 invididuals. All prediction models showed similarly good performance. The Harrell's C-index was close to 0.9 for all IHD models, and above 0.7 for stroke models. In IHD models, age, sex, high-density lipoprotein, low-density lipoprotein, cholesterol, and systolic blood pressure had higher importance, while in stroke models systolic blood pressure and age had higher importance. CONCLUSION: Our study analyzed classical regression and machine learning algorithms to develop cardiovascular disease risk prediction models for IHD and stroke in Japan that can be applied to practical use in a large population with predictive accuracy.

Quantum annealing and computation: challenges and perspectives.

In the introductory article of this theme issue, we provide an overview of quantum annealing and computation with a very brief summary of the individual contributions to this issue made by experts as well as a few young researchers. We hope the readers will get the touch of the excitement as well as the perspectives in this unusually active field and important developments there. This article is part of the theme issue 'Quantum annealing and computation: challenges and perspectives'.

Gender-specific Characteristics of Social Factors Related to Frequency of Daily Conversation Among Community-dwelling Older Adults: A Cross-sectional Observational Study.

Objectives: This study examined the social factors affecting the frequency of going out, and social isolation related to the frequency of daily conversation, stratified by gender. Method: The participants comprised 1,016 community-dwelling older Japanese adults, who were categorized into four groups: those who are (1) not isolated socially and go out every day, (2) not isolated socially and do not go out every day, (3) socially isolated and go out every day, and (4) socially isolated and do not go out every day. We performed a logistic regression analysis to assess the relationship between the frequency of daily conversation and the four groups. Results: Our multivariable logistic regression analysis (reference, group 1) showed that the coexistence of poor social factors significantly affected men (group 2: odds ratio [OR] 2.13 [1.10 to 4.12]; group 3: OR 2.92 [1.70 to 5.00]; and group 4: OR 4.28 [2.43 to 7.54]). For women, the frequency of going out was related to daily conversation only with social isolation group (group 2: OR 1.51 [0.77 to 2.98]; group 3: OR 2.42 [1.25 to 4.68]; and group 4: OR 3.81 [2.08 to 7.00]). Conclusion: Our findings suggest that promoting daily conversations of community-dwelling older adults can help prevent related health adversities.

Towards optimization of photonic-crystal surface-emitting lasers via quantum annealing.

Photonic-crystal surface-emitting lasers (PCSELs), which utilize a two-dimensional (2D) optical resonance inside a photonic crystal for lasing, feature various outstanding functionalities such as single-mode high-power operation and arbitrary control of beam polarizations. Although most of the previous designs of PCSELs employ spatially uniform photonic crystals, it is expected that lasing performance can be further improved if it becomes possible to optimize the spatial distribution of photonic crystals. In this paper, we investigate the structural optimization of PCSELs via quantum annealing towards high-power, narrow-beam-divergence operation with linear polarization. The optimization of PCSELs is performed by the iteration of the following three steps: (1) time-dependent 3D coupled-wave analysis of lasing performance, (2) formulation of the lasing performance via a factorization machine, and (3) selection of optimal solution(s) via quantum annealing. By using this approach, we discover an advanced PCSEL with a non-uniform spatial distribution of the band-edge frequency and injection current, which simultaneously enables higher output power, a narrower divergence angle, and a higher linear polarization ratio than conventional uniform PCSELs. Our results potentially indicate the universal applicability of quantum annealing, which has been mainly applied to specific types of discrete optimization problems so far, for various physics and engineering problems in the field of smart manufacturing.

Risk factors for small intestinal adenocarcinomas that are common in the proximal small intestine.

The frequency of primary small intestinal adenocarcinoma is increasing but is still low. Its frequency is approximately 3% of that of colorectal adenocarcinoma. Considering that the small intestine occupies 90% of the surface area of the gastrointestinal tract, small intestinal adenocarcinoma is very rare. The main site of small intestinal adenocarcinoma is the proximal small intestine. Based on this characteristic, dietary animal proteins/lipids and bile concentrations are implicated and reported to be involved in carcinogenesis. Since most nutrients are absorbed in the proximal small intestine, the effect of absorbable intestinal content is a suitable explanation for why small intestinal adenocarcinoma is more common in the proximal small intestine. The proportion of aerobic bacteria is high in the proximal small intestine, but the absolute number of bacteria is low. In addition, the length and density of villi are greater in the proximal small intestine. However, the involvement of villi is considered to be low because the number of small intestinal adenocarcinomas is much smaller than that of colorectal adenocarcinomas. On the other hand, the reason for the low incidence of small intestinal adenocarcinoma in the distal small intestine may be that immune organs reside there. Genetic and disease factors increase the likelihood of small intestinal adenocarcinoma. In carcinogenesis experiments in which the positions of the small and large intestines were exchanged, tumors still occurred in the large intestinal mucosa more often. In other words, the influence of the intestinal contents is small, and there is a large difference in epithelial properties between the small intestine and the large intestine. In conclusion, small intestinal adenocarcinoma is rare compared to large intestinal adenocarcinoma due to the nature of the epithelium. It is reasonable to assume that diet is a trigger for small intestinal adenocarcinoma.

The effect of care receivers' dysphagia severity on caregiver burden among family caregivers.

INTRODUCTION: Dysphagia has received much attention as a factor that affects caregiver burden. However, few studies have examined how its severity can affect caregiver burden. This study aimed to examine the effect of dysphagia severity on caregiver burden. METHODS: A cross-sectional online survey was carried out among family caregivers. We assessed caregiver burden using the Zarit Burden Interview. The dysphagia severity was assessed using the Functional Oral Intake Scale, and the caregivers were divided into three groups based on care receivers' oral intake status (levels 1-3: tube-feeding group; levels 4-6: texture-modified food group; level 7: normal group). To investigate the relationship between caregiver burden and dysphagia severity, univariable and multivariable logistic regression analyses were applied to caregiver burden. RESULTS: The Zarit Burden Interview was significantly higher in the texture-modified food group, and the proportions of high caregiver burden reached 25.2%, 39.5% and 23.4% in the normal group, texture-modified food group and tube-feeding group, respectively. The multivariable analyses applied to caregiver burden (reference, normal group) showed that the texture-modified food group was significantly associated with caregiver burden (OR 1.55, 95% CI 1.04-2.32), whereas the tube-feeding group had no relationship with caregiver burden (OR 0.68, 95% CI 0.31-1.49). CONCLUSIONS: Our study showed that the intake of texture-modified food significantly affected caregiver burden even after adjusting for confounding factors, whereas the use of tube feeding did not increase caregiver burden. These results suggest that it is necessary to consider dysphagia severity to reduce dysphagia-related caregiver burden. Geriatr Gerontol Int 2022; 22: 870-875.

Black pleural effusion caused by a pancreaticopleural fistula associated with autoimmune pancreatitis: A case report.

RATIONALE: Black pleural effusion is a rare medical condition and a diagnostic marker. Pancreaticopleural fistula is one of the causes of black pleural effusion. Thus far, black pleural effusions caused by pancreaticopleural fistulae have mostly been reported in patients with alcohol-induced chronic pancreatitis. In this report, we present a case of black pleural effusion caused by a pancreaticopleural fistula associated with autoimmune pancreatitis. PATIENT CONCERNS AND DIAGNOSIS: A 59-year-old female without a history of alcohol drinking presented to our hospital with a chief complaint of dyspnea, as well as chest and back discomfort. She had left pleural effusion, and thoracentesis showed black pleural effusion. Computed tomography revealed the presence of encapsulated fluid from the pancreatic tail to the left pleural cavity, which was diagnosed as a pancreaticopleural fistula. It also showed diffuse pancreatic swelling. Serum testing showed a high IgG4 level (363 mg/dL). These findings led to the diagnosis of autoimmune pancreatitis. INTERVENTIONS AND OUTCOME: The patient underwent endoscopic pancreatic sphincterotomy and pancreatic duct stent placement and received treatment with steroids. After treatment, there was no further accumulation of pleural effusion observed. CONCLUSION: This is the first report of black pleural effusion due to a pancreaticopleural fistula associated with autoimmune pancreatitis. The characteristic appearance of black pleural effusion may assist diagnosis. We report this case to emphasize that autoimmune pancreatitis can be a cause of black pleural effusion.

The effects of rehabilitation therapy duration on functional recovery of patients with subacute stroke stratified by individual's age: a retrospective multicenter study.

BACKGROUND: The duration of rehabilitation therapy is one of the key elements for promoting post-stroke functional recovery. However, whether an individual's age affects the effectiveness of the duration of rehabilitation therapy on post-stroke functional recovery remains unclear. AIM: This study aimed to investigate whether age has an influence on the relationship between the duration of rehabilitation therapy and post-stroke functional recovery. DESIGN: This is a retrospective observational study. SETTING: Six convalescent inpatient rehabilitation hospitals in Japan. POPULATION: The population of the study was represented by a total of 1186 participants with subacute stroke. METHODS: Participants were stratified into four groups according to their age (≤59, 60-69, 70-79, and ≥80 years). The data of minutes involved in performing rehabilitation therapy for participants during hospitalization per day (extracted from the medical records of each hospital). The outcome measurement was the absolute change in the functional independence measure (FIM) score during hospitalization. RESULTS: The mean FIM gains in the ≤59 years, 60-69 years, 70-79 years, and the ≥80 years groups were 38.7 (18.8), 32.8 (18.0), 29.7 (16.6), and 25.4 (17.2), respectively. The results of the multivariate regression analyses showed that there was a significant association between the duration of daily rehabilitation therapy and the FIM gain in the 70-79 years and the ≥80 years groups (-70-79 years group: B=1.289, ß=0.290, 95% confidence intervals (CIs): 0.718-1.859, P<0.001; the ≥80 years group: B=2.375, ß=0.371, 95% CIs: 1.644-3.107, P<0.001), but not in the other groups. CONCLUSIONS: For patients with subacute stroke in rehabilitation hospitals, a higher duration of daily rehabilitation therapy was associated with better functional recovery in the 70-79 years group and ≥80 years groups. Understanding the responsiveness of patients with stroke to rehabilitation therapy by age group helps to better allocate medical resources and develop more effective approaches. CLINICAL REHABILITATION IMPACT: An increased duration of daily rehabilitation therapy may be helpful in older adults with stroke selected for intensive rehabilitation for improvement of basic daily functioning.

Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing.

BACKGROUND: Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS). METHODS: We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining. RESULTS: The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors. CONCLUSIONS: SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations.