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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.

ABSTRACT 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.

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 (β = 0.05; 95% confidence interval [CI], -0.04–0.13, p=0.30) nor non‐steroidal anti‐inflammatory medications (β = 0.09; 95% CI, -0.02–0.19; p=0.10) were significantly associated with FILS score at discharge. Conclusions 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.

Abstract Background Recently, the Asian Working Group for Cachexia (AWGC) published a consensus statement on diagnostic criteria for cachexia in Asians. We aimed to validate the criteria in adult patients in Japan with advanced cancer. Methods We conducted a single‐institution retrospective cohort study between April 2021 and October 2022. The AWGC criteria include chronic comorbidities and either a weight loss of >2% over 3–6 months or a body mass index (BMI) of 2% in 6 months (87% vs. 14%, P 5 mg/L (85% vs. 56%, P

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.

Abstract Familial hypercholesterolemia (FH) is an inherited autosomal dominant disorder that is associated with a high plasma level of low-density lipoprotein (LDL) cholesterol, leading to an increased risk of cardiovascular diseases. To develop basic and translational research on FH, we here generated an FH model in a non-human primate (cynomolgus monkeys) by deleting the LDL receptor (LDLR) gene using the genome editing technique. Six LDLR knockout (KO) monkeys were produced, all of which were confirmed to have mutations in the LDLR gene by sequence analysis. The levels of plasma cholesterol and triglyceride were quite high in the monkeys, and were similar to those in FH patients with homozygous mutations in the LDLR gene. In addition, periocular xanthoma was observed only 1 year after birth. Lipoprotein profile analysis showed that the plasma very low-density lipoprotein and LDL were elevated, while the plasma high density lipoprotein was decreased in LDLR KO monkeys. The LDLR KO monkeys were also strongly resistant to medications for hypercholesterolemia. Taken together, we successfully generated a non-human primate model of hypercholesterolemia in which the phenotype is similar to that of homozygous FH patients.

RhoA is required in vascular smooth muscle cells to inhibit MAP4K4 and prevent abdominal aortic aneurysm formation.

Osteosarcopenia is a new definitional approach that can increase the risk of falls and fractures in elderly compared with that of osteoporosis and sarcopenia alone. However, biomarkers for osteosarcopenia have not been well identified. Thus, we aimed to explore the biomarkers of osteosarcopenia, including bone, muscle, and geriatric markers. Outpatients attending a frailty clinic were enrolled in the study. Osteosarcopenia was defined as the coexistence of osteoporosis and sarcopenia. Osteoporosis was defined according to the criteria of the Japan Osteoporosis Society. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus (2019). We selected 35 blood/serum pathological parameters, including bone, inflammation, nutritional, and aging markers for the study. Logistic regression analysis for osteosarcopenia was performed to explore the biomarkers of osteosarcopenia. Of the total 600 patients with a mean age of 76.6 years, 595 were enrolled in the registry during the study period. Logistic regression analysis for osteosarcopenia showed that elevated thyroid-stimulating hormone (TSH) (odds ratio [OR]:1.375; 95 % confidence interval [CI]: 1.092–1.731), bone-specific alkaline phosphatase (BAP) (OR: 1.059; 95 % CI: 1.002–1.120), and estimated glomerular filtration rate (eGFR) (OR: 1.029; 95 % CI: 1.007–1.053) increased the likelihood of osteosarcopenia. On the other hand, elevated 25-hydroxyvitamin D (25OHD) (OR: 0.905; 95 % CI: 0.841–0.974), blood urea nitrogen (BUN) (OR: 0.895; 95 % CI: 0.829–0.966) and K (OR: 0.241; 95 % CI: 0.081–0.717) decreased the likelihood of osteosarcopenia. It is worthwhile to examine these biomarkers for older adult outpatients attending a frailty clinic for screening osteosarcopenia. Further studies are needed to investigate the effects of other markers of bone metabolism.

Sarcopenic dysphagia (SD) is an emerging concern in geriatric medicine. This study aimed to identify the prevalence, progression, and distinct attributes of SD in patients in the Department of Geriatric Medicine. Older adult patients admitted between 2021 and 2022 were enrolled. The department conducts a comprehensive geriatric assessment (CGA) combined with a multidisciplinary team-based intervention, setting the standard for medical care. We diligently assessed the occurrence and development of dysphagia at both the admission and discharge phases. Of the 180 patients analyzed (38.9% male, mean age 86.0 ± 6.6 years), 22.8% were diagnosed with SD at admission, thrice the rate of other dysphagia variants. Only one patient had new-onset dysphagia during hospitalization, attributed to SD. Patients with SD showed a better recovery rate (18.9%) than those with other dysphagia types. Patients with diminished swallowing capacity had compromised nutritional profiles, diminished energy and protein consumption, and extended fasting durations. Although sarcopenia is a prevalent inducer of dysphagia in older adults, an integrated approach in geriatric medicine involving rehabilitation, nutrition, and dentistry is pivotal. Strategies rooted in CGA promise potential for addressing dysphagia.

Maternal effects on offspring viability significantly contribute to the productivity and resilience of exploited marine fish populations. The temporal trend of biomass of chub mackerel (Scomber japonicus) in the western North Pacific showed cyclic fluctuation patterns, but it has been rapidly increasing since 2011. Although there are several assumptions regarding the mechanisms of the population dynamics of this species in these waters, there is a contradiction in the effects of thermal environmental conditions on recruitment success. We explored the effects of maternal age and/or previous spawning experience on egg and offspring traits of captive chub mackerel in response to thermal conditions. Moreover, from the relationship between the growth rate and temperature experienced by captive fish, the experienced temperatures of wild specimens were assessed. The sizes of eggs spawned from females aged 1–3 years were negatively correlated with temperature, but the effects of maternal age on egg size and nutrition were significant with larger and nutrient-rich eggs spawned from 2- or 3-year-old females (repeat spawners) than those from 1-year-old females (first-time spawners) at a given temperature. Such temperature- and maternal-age-dependent egg traits reflected the standard length of first-feeding larvae. The effects of maternal age on the starvation tolerance of larvae after hatching and body sizes of first-feeding larvae were also evident in larvae derived from 3-year-old females showing longer starvation tolerance and larger body heights than those from 1-year-old females. Further, larvae derived from 3-year-old females grew significantly faster than those from 1-year-old females at the tested temperatures. The process of ontogenetic development and growth rate of captive specimens until age 25 days were positively correlated with temperature. Meanwhile, the estimated temperatures experienced by wild specimens until age 25 days ranged from 18.0 to 20.3°C. These findings suggested that there were opposing thermal responses between maternal and offspring traits of chub mackerel, but the temperatures experienced by the main recruit fish may be restricted within the range of temperatures available for spawning. We discuss the mechanisms of reproductive success of this species in accordance with the maternal spawning experience and thermal effects on life history traits.

The assessment of sarcopenia is part of the nutritional assessment index and is essential in stroke management. This study aimed to identify and validate cutoff values of temporal muscle thickness (TMT) measured using computed tomography to identify sarcopenia after acute stroke. The participants were patients with stroke aged ≥65 years who were admitted to rehabilitation units. The recruited patients were randomly divided into the calculation and validation cohort. In the calculation cohort, TMT cutoff values for identifying sarcopenia were calculated using receiver operating characteristic analysis. The obtained values were validated in the validation cohort using sensitivity and specificity. The calculation cohort included 230 patients (125 men, mean age, 77.2 ± 7.2 years), whereas the validation cohort included 235 patients (125 men, mean age, 76.4 ± 6.95 years). The TMT cutoff values for identifying sarcopenia and low skeletal muscle index were the same: 3.83 mm for men and 2.78 mm for women. The TMT cutoff value for identifying sarcopenia showed a sensitivity and specificity of 0.642 and 0.750, respectively, for men, and 0.660 and 0.567, respectively, for women. We identified a valid cutoff value of temporal muscle thickness for identifying sarcopenia after acute stroke. TMT is easy to measure and may be useful for the early detection of sarcopenia.

Low body mass index (BMI) is an independent predictor of prolonged hospital stay and mortality in patients with chronic obstructive pulmonary disease (COPD). However, to the best of our knowledge, no studies have examined the validity of Asian BMI cutoff values for classifying severity based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with acute COPD exacerbations. This study sought to validate whether Asian BMI cutoff values can accurately predict 30-day in-hospital mortality, length of stay, and 90-day readmission outcomes for patients with acute COPD exacerbations. The present retrospective cohort study was conducted using a large claims database created by the JMDC. Patients were classified into three groups according to the severity of low BMI assessed using Asian BMI cutoff values. As a result, 624 (29.4%) had severely low BMI, and 444 (20.9%) had moderately low BMI. The severity of low BMI, as assessed by the Asian BMI cutoff values used in the GLIM criteria, was independently associated with 30-day in-hospital mortality (moderately low BMI: HR, 1.87; 95% CI, 1.13–3.08; p = 0.014 and severely low BMI: HR, 2.55; 95% CI, 1.66–3.92; p < 0.001). The Asian BMI cutoff values used to classify the severity of malnutrition in the GLIM criteria are clinically functional for predicting the prognosis of patients with acute COPD exacerbations.

Rastrelliger brachysoma is a mariculture candidate species, but reproduction in captive fish has been problematic. This report examines the difference in the HPG axis, the neuroendocrine system and the development of reproductive tissues between captive vs. wild male R. brachysoma. The gonadosomatic index (GSI) of sexually mature male wild R. brachysoma was 1.12±0.34 and 1.94±0.26 during the non-breeding and breeding seasons, respectively. Captive R. brachysoma had a GSI of 1.88±0.17. All wild R. brachysoma were in the late spermatogenic stage irrespective of seasons. Immunostaining results showed that sbGnRH-immunoreactive neurons were distributed in three areas of the brain, namely the nucleus periventricularis, nucleus preopticus and nucleus lateralis tuberis. Follicle stimulating hormone and luteinizing hormone immunoreactivities were also observed in the pituitary gland. The levels of brain sbGnRH and GtH mRNA were not significantly different between the non-breeding and breeding seasons, but captive fish displayed (times or percent difference) lower mRNA levels than wild fish. These results suggest that these hormones control the testicular development in R. brachysoma and that the impaired reproduction in captivity may be due to their relative lower expression levels of follicle stimulating hormone and luteinizing hormone genes.

Background: The effect of sarcopenia on the recovery of swallowing function, and the interaction among sarcopenia, nutrition care, and rehabilitation therapy are inconclusive. Methods: This multicenter cohort study was conducted between November 2018 and October 2020 in convalescent rehabilitation hospitals in Japan and included post-stroke patients aged ≥65 years with dysphagia. All participants were assigned to sarcopenia and non-sarcopenia groups. The primary outcome was the achievement of ≥2 Food Intake Level Scale [FILS] gain, and the secondary outcomes included Functional Independence Measure (FIM) gain and efficiency. Considering the effect modification of energy intake and rehabilitation duration, logistic regression analyses were performed. Results: Overall, 153 participants with (median age, 82 years; 57.5% women) and 40 without (median age 75 years; 35.0% women) sarcopenia were included. The non-sarcopenia group had more patients who achieved an FILS gain of ≥2 (75.0%) than the sarcopenia group (51.0%). Sarcopenia was independently associated with a poor FILS gain (odds ratio:0.34, 95% confidence intervals: 0.13–0.86) but not associated with FIM gain or efficiency. This association was not affected by the rehabilitation duration or energy intake. Conclusions: In conclusion, sarcopenia was negatively associated with the recovery of swallowing function in stroke patients without interaction by energy intake and rehabilitation duration.

ABSTRACT Cardinal tetra Paracheirodon axelrodi and bloodfin tetra Aphyocharax anisitsi are two species of characids with high trade value as ornamental fish in South America. Although both species inhabit middle water layers, cardinal neon exhibits a tropical distribution and bloodfin tetra a subtropical one. Generally, these species are difficult to grow, so it becomes essential to know some key components of the neuroendocrine system to achieve their reproduction in captivity. Considering the importance of deepening the knowledge of the reproductive physiology through functional morphology, for the first time in this work we performed an anatomical, morphological and immunohistochemical analysis of the pituitary gland of these two species. In both species, a leptobasic type pituitary is found in the ventral zone of the hypothalamus and it is characterized by a neurohypophysis which has a well-developed pituitary stalk and a globular adenohypophysis. The pituitary components, characterized by histochemistry and immunohistochemistry, shows a distribution pattern of cells types similar to other teleost species, with only slight differences in the distribution of βFSH and βLH for P. axelrodi.

This cross-sectional study aimed to examine the accuracy of the Simplified Nutritional Appetite Questionnaire (SNAQ) and the SNAQ for Japanese Elderly (SNAQ-JE) for the Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition and sarcopenia screening in older persons. We included 380 inpatients aged ≥65 years (mean age, 79.3 ± 7.9; 60.0% women) and admitted to rehabilitation units. Undernutrition and sarcopenia were diagnosed based on GLIM criteria and the Asian Working Group for Sarcopenia, respectively, using bioimpedance analysis. Poor appetite was defined as an SNAQ score of

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This study assessed whether a high provided energy of ≥30 kcal/ideal body weight (IBW)/day (kg) for patients with sarcopenic dysphagia effectively improved swallowing ability and the activities of daily living (ADLs). Among 110 patients with sarcopenic dysphagia (mean age, 84.9 ± 7.4 years) who were admitted to a post-acute hospital, swallowing ability and the ADLs were assessed using the Food Intake LEVEL Scale (FILS) and the Functional Independence Measure (FIM), respectively. The primary outcome was the FILS at discharge, while the secondary outcome was the achievement of the FIM with a minimal clinically important difference (MCID) at discharge. We created a homogeneous probability model without statistically significant differences using the inverse probability of treatment weighting (IPTW) method with and without a mean provided energy of ≥30 kcal/IBW/day (kg) for a period of 1 week of hospitalization and compared the outcomes between groups. A mean provided energy of ≥30 kcal/IBW/day (kg) was achieved in 62.7% of patients. In the IPTW model, the FILS and the rates of achieved MCID of the FIM at discharge were significantly higher in the mean provided energy of ≥30 kcal/IBW/day (kg) group (p = 0.004 and p < 0.001, respectively). A high provided energy for patients with sarcopenic dysphagia may improve swallowing ability and produce clinically meaningful functional outcomes.

Malnutrition negatively affects the quality of life of patients with dysphagia. Despite the need for nutritional status assessment in patients with dysphagia, standard, effective nutritional assessments are not yet available, and the identification of optimal nutritional assessment items for patients with dysphagia is inadequate. We conducted a scoping review of the use of nutritional assessment items in adult patients with oropharyngeal and esophageal dysphagia. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched to identify articles published in English within the last 30 years. Twenty-two studies met the inclusion criteria. Seven nutritional assessment categories were identified: body mass index (BMI), nutritional screening tool, anthropometric measurements, body composition, dietary assessment, blood biomarkers, and other. BMI and albumin were more commonly assessed in adults. The Global Leadership Initiative on Malnutrition (GLIM), defining new diagnostic criteria for malnutrition, includes the categories of BMI, nutritional screening tool, anthropometric measurements, body composition, and dietary assessment as its required components, but not the blood biomarkers and the “other” categories. We recommend assessing nutritional status, including GLIM criteria, in adult patients with dysphagia. This would standardize nutritional assessments in patients with dysphagia and allow future global comparisons of the prevalence and outcomes of malnutrition, as well as of appropriate interventions.

Osteopenia/osteoporosis and sarcopenia are common geriatric diseases among older adults and harm activities of daily living (ADL) and quality of life (QOL). Osteosarcopenia is a unique syndrome that is a concomitant of both osteopenia/osteoporosis and sarcopenia. This review aimed to summarize the related factors and clinical outcomes of osteosarcopenia to facilitate understanding, evaluation, prevention, treatment, and further research on osteosarcopenia. We searched the literature to include meta-analyses, reviews, and clinical trials. The prevalence of osteosarcopenia among community-dwelling older adults is significantly higher in female (up to 64.3%) compared to male (8–11%). Osteosarcopenia is a risk factor for death, fractures, and falls based on longitudinal studies. However, the associations between osteosarcopenia and many other factors have been derived based on cross-sectional studies, so the causal relationship is not clear. Few studies of osteosarcopenia in hospitals have been conducted. Osteosarcopenia is a new concept and has not yet been fully researched its relationship to clinical outcomes. Longitudinal studies and high-quality interventional studies are warranted in the future.

Geriatric patients with hip fractures often experience overlap in problems related to nutrition, including undernutrition, sarcopenia, and frailty. Such problems are powerful predictors of adverse responses, although few healthcare professionals are aware of them and therefore do not implement effective interventions. This review aimed to summarize the impact of undernutrition, sarcopenia, and frailty on clinical outcomes in elderly individuals with hip fractures and identify successful strategies that integrate nutrition and rehabilitation. We searched PubMed (MEDLINE) and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant literature published over the last 10 years and found that advanced interventions targeting the aforementioned conditions helped to significantly improve postoperative outcomes among these patients. Going forward, protocols from advanced interventions for detecting, diagnosing, and treating nutrition problems in geriatric patients with hip fractures should become standard practice in healthcare settings.

The study aimed to investigate the impact of physical intervention and the amount of nutritional intake on the increase in tongue strength and swallowing function in older adults with sarcopenia. From November 2018 and May 2019, older patients with sarcopenia who were admitted for rehabilitation were analyzed. The intervention employed in the study was the usual physical and occupational therapy for two months. Tongue strength was measured before and after two months of treatment. Data on tongue strength, the amount of energy and protein intake, intervention time, and swallowing function were examined. A total of 95 sarcopenic older patients were included (mean age 83.4 ± 6.5 years). The mean tongue strength after the intervention was significantly increased from 25.4 ± 8.9 kPa to 30.5 ± 7.6 kPa as a result of the treatment (p < 0.001). After adjusting the confounding factors in the multivariable models, an energy intake of ≥30 kcal/kg/day and a protein intake of ≥1.2 g/kg/day based on the ideal body weight had a significant impact on the increase in tongue strength after the treatment (p = 0.011 and p = 0.020, respectively). Swallowing function assessed using the Mann Assessment of Swallowing Ability was significantly increased after the treatment (mean difference between pairs: 1.12 [0.53–1.70]; p < 0.001). Physical intervention and strict nutritional management for older inpatients with sarcopenia could be effective to improve tongue strength and swallowing function.

The purpose of this study was to investigate a means by which to reflect muscle mass using chest computed tomography (CT). A cross-sectional study was conducted with patients aged ≥ 65 years having abdominal and chest CT scans. The formula to predict third lumbar vertebra (L3) cross-sectional area (CSA) of the muscles from the erector muscles of the spine at the twelfth thoracic vertebra (Th12) level slice on CT was created using the five-fold cross-validation method. Correlation between predicted L3 CSA and measured L3 CSA of the muscles was assessed by intraclass correlation coefficients (ICC) and correlation coefficients (r) in the data of the development, and predictability was examined with accuracy and F-values in the validation study. The development study included 161 patients. The developed formula was as follows: −1006.38 + 16.29 × age [years] + 1161.80 × sex (if female, 0; if male, 1) + 55.91 × body weight [kg] + 2.22 × CSA of the erector muscles at Th12 [mm2]. The formula demonstrated strong concordance and correlation (ICC = 0.849 [0.800–0.887] and r = 0.858 [0.811–0.894]). The validation study included 34 patients. The accuracy and F-value between predicted CSA and measured CSA were high (accuracy = 0.889–0.944, F-value = 0.931–0.968). We developed a formula predicting CSA at L3 using Th12 CT slice. This formula could be used to assess decreased muscle mass even with chest CT alone.

This study aimed to investigate the association between the development of dysphagia in patients with underlying sarcopenia and the prevalence of sarcopenic dysphagia in older patients following surgical treatment for hip fracture. Older female patients with hip fractures (n = 89) were studied. The data of skeletal muscle mass, hand-grip strength, and nutritional status were examined. The development of dysphagia postoperatively was graded using the Food Oral Intake Scale by a certified nurse in dysphagia nursing. The patients’ mean age was 85.9 ± 6.5 years. The prevalence of sarcopenia was 76.4% at baseline. Of the 89 patients, 11 (12.3%) and 12 (13.5%) had dysphagia by day 7 of hospitalization and at discharge, respectively. All patients who developed dysphagia had underlying sarcopenia. Lower skeletal muscle mass index (SMI) (2) and grip strength (p = 0.003 and Phi = 0.391) and at discharge (p = 0.001 and Phi = 0.448). Dysphagia developed after hip fracture surgery could be sarcopenic dysphagia, and worsening sarcopenia was a risk factor for dysphagia following hip fracture surgery. Clinicians and medical coworkers should become more aware of the risks of sarcopenic dysphagia. Early detection and preventive interventions for dysphagia should be emphasized.

Malnutrition leads to poor prognoses, including a predisposition to falls. Few studies have investigated the relationship between malnutrition and falls during hospitalization. This study aimed to determine malnutrition’s association with falls during hospitalization. A retrospective observational study was conducted. Patients aged ≥65 years that were admitted to and discharged from a university hospital between April 2018 and March 2019 were examined. Patients with independent basic activities of daily living were included. Diagnosis of malnutrition was based on the European Society for Clinical Nutrition and Metabolism (ESPEN) criteria at admission. Disease information such as the Charlson Comorbidity Index (CCI) and reasons for hospitalization were reviewed. Kaplan−Meier curve and multivariate Cox regression analyses were performed. Data from 6081 patients (mean age: 74.4 ± 6.1 years; males: 58.1%) were analyzed. The mean CCI was 2.3 ± 2.8 points. Malnutrition was detected in 668 (11.0%) and falls occurred in 55 (0.9%) patients. Malnourished patients experienced a higher fall rate than those without malnutrition (2.4% vs. 0.7%, log-rank test p < 0.001). In multivariate analysis, malnutrition had the highest hazard ratio for falls among covariates (hazard ratio 2.78, 95% confidence interval 1.51−5.00, p = 0.001). In conclusion, malnutrition at the time of admission to hospital predicts in-hospital falls.

The study aimed to investigate the impact of sarcopenia and sarcopenia-related conditions on the development of swallowing disorders during hospitalization. Older adult inpatients (n = 8768) without swallowing disorders in the premorbid period were studied. Sarcopenia-related conditions were evaluated in terms of nutritional status, physical status, and ambulatory conditions as well as hand-grip strength and muscle mass assessed by calf circumference. Development of swallowing disorders was defined based on food texture at discharge from the hospital. The patients’ mean age was 76.1 ± 6.9 years. A total of 374 (4.3%) patients developed swallowing disorders during hospitalization. They were older, with poorer nutritional status, and had more decline of physical performance than those without swallowing disorders. Performance Status score (odds ratio (OR) = 1.28 (1.12−1.46) p < 0.001), ambulatory dependency (OR = 1.72 (1.09−2.71), p = 0.020), malnutrition score (OR = 0.92 (0.87−0.97), p = 0.002), insufficient nutritional intake (OR = 2.33 (1.60−3.40), p < 0.001), and length of stay (OR = 1.01 (1.00−1.01), p = 0.001) were independent contributing factors for swallowing disorder development in the multivariate analysis. The presence of possible sarcopenia was also a contributor to swallowing disorder development. In conclusion, swallowing disorders could develop in patients with possible sarcopenia and sarcopenia-related conditions during hospitalization. Clinicians should be aware of this risk and provide appropriate interventions to prevent sarcopenic dysphagia.

Neuropilin-1 (NRP1) has been identified as a VEGF-A receptor. DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1. In the present study, the RNA interference of VEGF-A or NRP1 suppressed DJM-1 cell proliferation. Furthermore, the overexpression of the NRP1 wild type restored shNRP1-treated DJM-1 cell proliferation, whereas NRP1 cytoplasmic deletion mutants did not. A co-immunoprecipitation analysis revealed that VEGF-A induced interactions between NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and Syx, a RhoGEF. The knockdown of GIPC1 or Syx reduced active RhoA and DJM-1 cell proliferation without affecting the MAPK or Akt pathway. C3 exoenzyme or Y27632 inhibited the VEGF-A-induced proliferation of DJM-1 cells. Conversely, the overexpression of the constitutively active form of RhoA restored the proliferation of siVEGF-A-treated DJM-1 cells. Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor. A cell-penetrating oligopeptide that targeted GIPC1/Syx complex formation inhibited the VEGF-A-induced activation of RhoA and suppressed DJM-1 cell proliferation. In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.

Neurofibromatosis type 2 (NF2) is an autosomal-dominant multiple neoplasia syndrome that results from mutations in the NF2 tumor suppressor gene. Patients with NF2 develop hallmark schwannomas that require surgery or radiation, both of which have significant adverse effects. Recent studies have indicated that the tumor microenvironment—in particular, tumor blood vessels—of schwannomas may be an important therapeutic target. Furthermore, although much has been done to understand how merlin, the NF2 gene product, functions as a tumor suppressor gene in schwannoma cells, the functional role of merlin in the tumor microenvironment and the mechanism(s) by which merlin regulates angiogenesis to support schwannoma growth is largely unexplored. Here we report that the expression of semaphorin 3F (SEMA3F) was specifically downregulated in schwannoma cells lacking merlin/NF2. When we reintroduced SEMA3F in schwannoma cells, we observed normalized tumor blood vessels, reduced tumor burden, and extended survival in nude mice bearing merlin-deficient brain tumors. Next, using chemical inhibitors and gene knockdown with RNA interference, we found that merlin regulated expression of SEMA3F through Rho GTPase family member Rac1. This study shows that, in addition to the tumor-suppressing activity of merlin, it also functions to maintain physiological angiogenesis in the nervous system by regulating antiangiogenic factors such as SEMA3F. Restoring the relative balance of proangiogenic and antiangiogenic factors, such as increases in SEMA3F, in schwannoma microenvironment may represent a novel strategy to alleviate the clinical symptoms of NF2-related schwannomas.

Vascular endothelial growth factors (VEGFs) include five molecules (VEGF-A, -B, -C, -D, and placental growth factor), and have various roles that crucially regulate cellular functions in many kinds of cells and tissues. Intracellular signal transduction induced by VEGFs has been extensively studied and is usually initiated by their binding to two classes of transmembrane receptors: receptor tyrosine kinase VEGF receptors (VEGF receptor-1, -2 and -3) and neuropilins (NRP1 and NRP2). In addition to many established results reported by other research groups, we have previously identified small G proteins, especially Ras homologue gene (Rho) and Ras-related protein (Rap), as important mediators of VEGF-A-stimulated signaling in cancer cells as well as endothelial cells. This review article describes the VEGF-A-induced signaling pathways underlying diverse cellular functions, including cell proliferation, migration, and angiogenesis, and the involvement of Rho, Rap, and their related molecules in these pathways.