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Background: Acute decompensated heart failure (ADHF) leads to hospitalizations and functional decline in older adults. Although cardiac rehabilitation (CR) is effective for stable heart failure, its impact on ADHF patients, particularly those without frailty, is unclear., Objectives: The goal of this study was to evaluate the efficacy and safety of early in-hospital CR for patients hospitalized with ADHF who are not frail., Methods: In this multicenter trial (ACTIVE-ADHF [Effects of Acute Phase Intensive Exercise Training in Patients with Acute Decompensated Heart Failure]), ADHF patients without physical frailty were randomized 2:1 to undergo either exercise-based CR or standard care. The intervention included early mobilization and structured exercise training. The primary outcome was the change in 6-minute walk distance (6MWD) from baseline to discharge. Secondary outcomes assessed physical and cognitive function, quality of life, and safety., Results: A total of 91 patients were randomized to treatment, with 59 allocated to the intervention group and 32 to the control group. The primary outcome, 6MWD, improved significantly more in the intervention group, with a mean increase of 75.0 ± 7.8 m vs 44.1 ± 10.2 m in the control group, with an effect size of 30.9 ± 13.1 m (95% CI: 4.8-57.0; P = 0.021). The intervention group showed favorable results in secondary efficacy outcomes, including physical and cognitive function, physical activity, and quality of life. Safety outcomes were similar between groups, except for a greater reduction in B-type natriuretic peptide levels at 90 days' postdischarge in the intervention group., Conclusions: In patients with ADHF without physical frailty, in-hospital exercise-based CR led to significant improvements in 6MWD at 2 weeks after randomization without compromising safety. (ACTIVE-ADHF [Effects of Acute Phase Intensive Exercise Training in Patients with Acute Decompensated Heart Failure]; UMIN000020919)., Competing Interests: Funding Support and Author Disclosures This work was partially supported by JSPS KAKENHI (grant numbers 15K16368 and 21H03309) and the Japanese Physical Therapy Association. Dr Kamiya has received funding outside of the submitted work from Eiken Chemical CO, Ltd and SoftBnak Corporation. Dr Yamashita holds company stock (<5% of the total) and has received a salary as one of the directors of an employer. Dr Matsue has received an honorarium from Otsuka Pharmaceutical Co, Novartis Pharma KK, Bayer Inc, and AstraZeneca; and has received research grants from Pfizer Japan Inc, Otsuka Pharmaceutical Co, EN Otsuka Pharmaceutical Co, Ltd, and Nippon Boehringer Ingelheim Co, Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Huntingtin-associated protein 1 (HAP1) is an essential constituent of the stigmoid body (STB) and is known as a neuroprotective interactor with causal agents for several neurodegenerative disorders, including huntingtin (HTT) in Huntington's disease. Previous in vitro studies showed that compared to normal HTT, STB/HAP1 exhibited a higher binding affinity for mutant HTT. The detailed in vivo relationships of STB/HAP1 with endogenous HTT, however, have not been clarified yet. This study examined the distribution of endogenous HTT and its relationships with STB/HAP1 in the adult mouse brain and spinal cord using light/fluorescence microscopy. Our results show that HTT immunoreactivity is highly distributed in the striatum, medial septal nucleus (MS), nucleus of the horizontal limb/ vertical limb of the diagonal band of Broca (HDB, VDB), substantia innominata basal part (SIB), pedunculopontine tegmental nucleus (PPTg), laterodorsal tegmental nucleus (LDTg), autonomic preganglionic neurons, and brainstem/spinal motoneurons. More than 90 % of HTT-immunoreactive (ir) neurons contain STB/HAP1 immunoreactivity in MS, VBD/HDB, SIB, PPTg, LDTg, and autonomic preganglionic nuclei. HTT-ir neurons in the striatal and motor nuclei, however, do not exhibit HAP1 immunoreactivity. These suggest that due to the absence of STB/HAP1-protectivity, HTT-ir striatal/motor neurons are more vulnerable to neurodegeneration than other HAP1-expressing HTT neurons. Our current findings might provide a framework for elucidating the pathophysiological functions of endogenous HTT and HAP1 in the central nervous system., Competing Interests: Declaration of Competing Interest The authors state that any known competing financial interests or personal relationships could have influenced none of the work described in this study., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients with cardiovascular disease (CVD) are often contending with various comorbidities including cognitive decline. Cognitive decline is a risk marker for adverse outcomes in these patients. On the other hand, cardiovascular rehabilitation (CVR) improves clinical outcomes. However, it remains uncertain whether CVR is associated with favorable outcomes in patients with CVD and cognitive decline. Therefore, the present study aimed to investigate whether CVR is associated with favorable outcomes in patients with CVD and cognitive decline., Methods: We reviewed 4232 patients admitted for CVD. Cognitive function was assessed using the Mini-Cog at hospital discharge, and a score of <3 was defined as cognitive decline. We measured the 6-min walking distance (6MWD) at discharge and 5 months after CVR prescription for participants in outpatient CVR. The primary outcome was change in exercise tolerance (Δ6MWD), and the secondary outcome was composite events (all-cause death and/or re-admission due to CVD). We compared Δ6MWD between patients with and without cognitive decline and examined the association between outpatient CVR participation and composite events., Results: Of all patients, 768 had cognitive decline. There was no significant difference in Δ6MWD between the cognitive decline and non-cognitive decline groups, even after adjusting for confounders [estimated mean difference: 2.20 m; 95 % confidence interval (CI): -0.60-5.00 m]. Additionally, participation in outpatient CVR was associated with lower rate of composite events, regardless of cognitive decline [adjusted hazard ratio (aHR): 0.589; 95 % CI: 0.552-0.627 in the cognitive decline group and aHR: 0.767; 95 % CI: 0.742-0.793 in the non-cognitive decline group]. An interaction was observed based on the presence of cognitive decline (p = 0.011)., Conclusion: Regardless of cognitive decline, participation in outpatient CVR was associated with increased exercise tolerance. Furthermore, outpatient CVR was linked to reduced composite events in both, with particularly potent association in cognitively impaired patients., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Patients with heart failure (HF) often suffer from hepato-renal dysfunction. The associations between hepato-renal function changes and mortality remain unclear. Further, the effect of cardiac rehabilitation (CR) on mortality and motor functions in patients with HF and hepato-renal dysfunction requires investigation., Methods: We reviewed 2522 patients with HF (63.2 % male; median age: 74 years). The association between changes in hepato-renal function assessed by the Model for End-stage Liver Disease eXcluding INR (MELD-XI) score and mortality was examined. The association of CR participation with mortality and physical functions was investigated in patients with HF with decreased, unchanged, and increased MELD-XI scores., Results: During the follow-up period, 519 (20.6 %) patients died. Worsened MELD-XI score was independently associated with all-cause death [adjusted hazard ratio (aHR): 1.099; 95 % confidence interval (CI): 1.061-1.138; p < 0.001]. CR participation was associated with low mortality, even in the increased MELD-XI score group (aHR: 0.498; 95 % CI: 0.333-0.745; p < 0.001). Trajectory of the MELD-XI score was not associated with physical function changes. There were no time by MELD-XI score interaction effects on handgrip strength (p = 0.084), leg strength (p = 0.082), walking speed (p = 0.583), and 6-min walking distance (p = 0.833) in patients participating in outpatient CR., Conclusions: Hepato-renal dysfunction predicts high mortality. CR participation may be helpful for a better prognosis of patients with HF and hepato-renal dysfunction., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Diagnosing sarcopenia in heart failure (HF) patients is important, but how to assess skeletal muscle mass in HF patients with fluid retention is controversial. We aimed to examine the association between sarcopenia, defined by different skeletal muscle mass measurements, and clinical outcomes in older HF patients., Methods: We included 546 older HF patients (≥ 65 years) who were assessed for sarcopenia at discharge (median age 77 years, 309 males). Sarcopenia was diagnosed using grip strength, usual gait speed, and skeletal muscle mass according to international criteria. We used mid-upper arm circumference (MUAC), mid-upper arm muscle circumference (MAMC), calf circumference (CC), and skeletal muscle mass index (SMI) assessed by bioelectrical impedance analysis to assess skeletal muscle mass and defined sarcopenia in each of these measurements. Prognostic outcomes were composite events (all-cause death and HF rehospitalization) and cardiovascular disease (CVD) events (CVD death and CVD rehospitalization). Quality of life (QOL) was assessed using the 36-item Short-Form Health Survey physical functioning (SF-36PF) score., Results: The sarcopenia defined by MUAC [hazard ratio (HR): 2.50; 95 % confidence interval (95 % CI): 1.64-3.81; p < 0.001] or MAMC (HR: 1.98; 95 % CI: 1.35-2.92; p = 0.001) were associated with higher composite event rates than the non-sarcopenia. The sarcopenia defined by MUAC (HR: 1.88; 95 % CI: 1.25-2.83; p = 0.002) or MAMC (HR: 1.70; 95 % CI: 1.16-2.49; p = 0.007) were associated with higher CVD event rates than the non-sarcopenia. The sarcopenia defined by CC or SMI were not associated with prognoses. The sarcopenia defined by MUAC, MAMC, or CC were associated with low SF-36PF scores (all p < 0.05)., Conclusions: These results suggest that a diagnosis of sarcopenia based on MUAC or MAMC rather than CC or SMI reflects prognosis and QOL in older HF patients., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Sarcopenia in patients with heart failure (HF) is associated with poor prognosis. Cardiac rehabilitation (CR) decreases the incidence of adverse events in patients with HF. However, the clinical implications of improving sarcopenia status through CR remain unclear. This study investigated the relationship between the changes in sarcopenia status in patients with HF undergoing outpatient CR and the risk of mortality and adverse events., Design: This was a retrospective cohort study of patients hospitalized at the Kitasato University Hospital Cardiovascular Center for the treatment of HF between January 2007 and December 2020., Setting and Participants: Patients with HF whose sarcopenia status was assessed at hospital discharge and following at least 3 months of outpatient CR were included. Based on the sarcopenia status, all patients were divided into 3 groups: patients without sarcopenia at discharge (ie, robust), patients with sarcopenia at discharge but no sarcopenia following CR (ie, improved), and patients with sarcopenia at discharge and following CR (ie, unimproved)., Methods: Cox regression analysis was used to examine the risk of all-cause death associated with the 3 sarcopenia status groups., Results: Of 546 patients with HF (median age: 70 years; male: 63.6%), 377 (69.0%), 54 (9.9%), and 115 (21.1%) were classified as robust, improved, and unimproved, respectively. Multivariate Cox regression analysis showed that the unimproved group had a significantly greater risk of all-cause death when compared to the robust group [hazard ratio (HR) 2.603, 95% CI 1.375-4.930, P = .004], but it did not differ from the improved group (HR 1.403, 95% CI 0.598-3.293, P = .43)., Conclusions and Implications: No improvement in sarcopenia status in patients with HF undergoing outpatient CR was associated with a higher risk of all-cause death. Sarcopenia may be an important target to improve the prognosis of patients with HF., Competing Interests: Disclosure K.K. received funding outside the submitted work from Eiken Chemical Co, Ltd and SoftBank Cor Ltd. The other authors have no conflicts of interest to declare., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The most recommended treatment for stage IV EGFR-positive lung cancer is osimertinib monotherapy. The dosage of osimertinib is fixed at 80 mg/day regardless of body surface area (BSA), however some patients withdraw or reduce the dosage due to adverse events (AEs)., Methods: We performed a retrospective cohort study of 98 patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who received 80 mg osimertinib as the initial treatment. We investigated the impact of BSA on efficacy and safety of osimertinib., Results: The cut-off value of BSA was estimated using the receiver operating characteristics curve, and was determined to be 1.5 m 2 . There were 44 patients in the BSA < 1.5 group and 54 patients in the BSA ≥ 1.5 group. There was no significant difference in the incidence of AEs (hematologic toxicity of ≥grade 3 or higher, and non-hematologic toxicity of ≥grade 3) between the two groups. However, the incidence of dose reduction due to AEs was significantly higher in the BSA < 1.5 group compared with the BSA ≥ 1.5 group (16 patients vs 5 patients, p = 0.003). The main reasons were fatigue, anorexia, diarrhea, and liver disfunction. Median progression-free survival (PFS) was not significantly different (16.9 months in the BSA < 1.5 group vs 18.1 months in the BSA ≥ 1.5 group, p = 0.869)., Conclusion: Differences in BSA affected the optimal dose of osimertinib. However, the PFS with osimertinib treatment was not affected by BSA. Therefore, when using osimertinib as an initial treatment for patients with EGFR-mutant NSCLC, dose reduction to control AEs should be considered, especially in the BSA<1.5 group., Competing Interests: Declaration of competing interest Motohiro Tamiya has received lecture fees from Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Novartis, Pfizer, Asahi Kasei Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Bayer, Amgen, Kyowa-Kirin, and Nippon Kayaku. Kei Kunimasa has received lecture fees from AstraZeneca, Chugai Pharma and Novartis. Kazumi Nishino has received lecture fees from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Roche Diagnostics, Novartis, Pfizer, Merk, Janssen Pharmaceutical K.K., Bristol Myers Squibb, and Nippon Kayaku. Mari Takagi has received lecture fees from Eli Lilly, Yakult, Terumo, Chugai Pharmaceutical, Towa Pharmaceutical, Daiichi-Sankyo, Becton Dickinson and Company, MSD, Taiho Pharmaceutical, Nippon Kayaku, AstraZeneca, Sando, and Ono Pharmaceutical. Other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Background: This study aimed to evaluate the effects of orthogeriatric co-management of hip fractures at a regional core hospital., Methods: This study included patients with proximal hip fracture. Patients were divided into two groups, conventional multidisciplinary group I including patients attending the hospital between April 2015 and March 2016 and orthogeriatric group II including patients attending the hospital between April 2016 and March 2017, which were compared retrospectively. In the control group, the conventional multidisciplinary team treated patients as whole-body controls. In the intervention group, the newly recruited geriatricians performed physical examinations, laboratory tests, radioactive imaging, and physiological tests. Furthermore, they consulted ward pharmacists, rigorously conducted positive polypharmacy interventions , and evaluated the type and number of mediated drugs on admission., Results: The number of medicated drugs significantly decreased from 6.03 ± 4.3 on admission to 5.50 ± 3.59 on discharge in group II, whereas group I did not show a significant decrease. Despite the more number of hospitalized patients in group II (166 patients) than in group I (126 patients), the recovery rate from postoperative urinary retention increased significantly from 57.8% (19/30) in group I to 84.3% (32/59) in group II (p = 0.049), while the incidence of aspiration pneumonia decreased from 7.1% (9/126) in group I to 2.49% (4/166) in group II (p = 0.08). The patients received six or more prescribed drugs on admission, and the number remained constant. However, the number of medicated drugs on discharge showed a marginally significant decrease from 6.03 ± 4.3 in group I to 5.50 ± 3.59 in group II (p < 0.05)., Conclusions: Compared to the conventional multidisciplinary group, the orthogeriatric team contributed to reducing the number of multi-effect drugs and perioperative complications without negatively affecting mortality despite the increased number of patients. The in-hospital mortality rate did not change between the groups. The orthogeriatric program succeeded in preventing and treating perioperative complications., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background Aims: Stroke is a frequently observed neurological disorder that might lead to permanent and severe disability. Recently, various regenerative therapies have been developed, some of which have already been applied clinically. However, their outcomes have not been fully satisfactory. In particular, the development of regenerative therapies for chronic ischemic stroke is greatly needed. Herein intracerebral administration of bone marrow-derived mononuclear cells (BM-MNCs) was assessed as a potential treatment for chronic ischemic stroke using a severe combined immunodeficiency mouse model characterized by minimal vascular variation unrelated to immunodeficiency., Methods: A reproducible model of permanent middle cerebral artery occlusion was prepared, and intracerebral BM-MNC transplantation was performed 14 days after stroke induction in the infarcted brain., Results: Sensorimotor behavioral function and cerebral blood flow were significantly improved upon treatment with BM-MNCs compared to control medium injection. The transplanted cells exhibited characteristics of the vascular endothelium and microglia/macrophages. Significant angiogenesis and suppression of astrogliosis and microgliosis were observed in the affected brain. Messenger RNA expression analysis showed significant increases in anti-inflammatory cytokines, A2 astrocyte/anti-inflammatory microglia markers and vascular endothelial markers such as vascular endothelial growth factor and significant decreases in pro-inflammatory cytokines and A1 astrocyte/pro-inflammatory microglia markers following BM-MNC transplantation., Conclusions: These results suggest that intracerebral administration of BM-MNCs should be considered an effective cell therapy for chronic stroke., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia is associated with risks of various adverse outcomes, and the assessment of skeletal muscle mass is necessary for its diagnosis. However, heart failure (HF) is a syndrome characterised by fluid retention, which affects muscle mass measurements. Different measurement methods have been reported to have different prognostic implications. We investigated the association between skeletal muscle mass metrics measured with the use of bioelectrical impedance analysis (BIA) and anthropometric measures and prognosis in patients with HF., Methods: The findings of 869 consecutive patients with HF were reviewed. We investigated the skeletal muscle mass index (SMI) measured with the use of BIA, the mid-upper arm circumference (MUAC), the arm muscle circumference (AMC), and the calf circumference (CC), and the patients were divided into 3 groups according to the sex-specific tertiles of the skeletal muscle mass metrics. The end points were all-cause death and readmission due to HF., Results: The high MUAC and AMC groups showed significantly better prognoses than their respective low groups (combined events: high MUAC group hazard ratio [HR] 0.559, 95% confidence interval [CI] 0.395-0.789 [P < 0.01]; high AMC group HR 0.505, 95% CI 0.359-0.710 [P < 0.01]), although high SMI and high CC were not associated with better prognoses., Conclusions: Among patients with HF, MUAC and AMC are more associated with prognosis than SMI and CC, which are recommended in preexisting sarcopenia guidelines. MUAC and AMC may also be useful measures in sarcopenia assessments., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: This study was conducted to verify whether serum cholinesterase (ChE) is useful in predicting prognosis and discriminating undernutrition status compared to existing low-nutrition indices of blood chemical tests in patients with heart failure (HF)., Methods and Results: A total of 1617 patients (1204 older patients) with HF who evaluated ChE during hospitalization were recruited for this study. The primary outcome was all-cause death, and multivariate survival analysis was performed. We drew a receiver operating characteristic curve for all-cause death, some undernutrition status, such as low body mass index, thin mid-upper arm circumference, low grip strength, and slow gait speed. The area under the curve was used to compare the predictive ability of ChE with some existing nutritional parameters, such as blood biochemical tests, controlling nutritional status (CONUT), and the geriatric nutritional risk index (GNRI). After adjusting for 29 variables, higher ChE significantly decreased the risk of all-cause death (per 10 increase, hazard ratio: 0.975, 95% confidence interval: 0.952-0.998), and this trend was maintained for older patients (per 10 increase, hazard ratio: 0.972, 95% confidence interval: 0.947-0.997). ChE was moderately correlated with CONUT and GNRI, but the predictive ability for all-cause death was higher for ChE relative to both scores. ChE tended to have an almost consistently high predictive ability compared with other blood biochemical tests., Conclusions: ChE was associated with all-cause death and an almost consistently higher predictive ability for all-cause death and undernutrition status in comparison to existing blood chemical tests and nutritional scores., Competing Interests: Conflicts of interest Mr. Kamiya has received research funding from Eiken Chemical Co., Ltd. The other authors have nothing to declare., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The fluid nature of lipid bilayers is indispensable for the dynamic regulation of protein function and membrane morphology in biological membranes. Membrane-spanning domains of proteins interact with surrounding lipids and alter the physical properties of lipid bilayers. However, there is no comprehensive view of the effects of transmembrane proteins on the membrane's physical properties. Here, we investigated the effects of transmembrane peptides with different flip-flop-promoting abilities on the dynamics of a lipid bilayer employing complemental fluorescence and neutron scattering techniques. The quasi-elastic neutron scattering and fluorescence experiments revealed that lateral diffusion of the lipid molecules and the acyl chain motions were inhibited by the inclusion of transmembrane peptides. The neutron spin-echo spectroscopy measurements indicated that the lipid bilayer became more rigid but more compressible and the membrane viscosity increased when the transmembrane peptides were incorporated into the membrane. These results suggest that the inclusion of rigid transmembrane structures hinders individual and collective lipid motions by slowing down lipid diffusion and increasing interleaflet coupling. The present study provides a clue for understanding how the local interactions between lipids and proteins change the collective dynamics of the lipid bilayers, and therefore, the function of biological membranes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Huntingtin-associated protein 1(HAP1) is an immunohistochemical marker of the stigmoid body (STB). Brain and spinal cord regions with lack of STB/HAP1 immunoreactivity are always neurodegenerative targets, whereas STB/HAP1 abundant regions are usually spared from neurodegeneration. In addition to the brain and spinal cord, HAP1 is abundantly expressed in the excitatory and inhibitory motor neurons in myenteric plexuses of the enteric nervous system (ENS). However, the detailed expression of HAP1 and its neurochemical characterization in submucosal plexuses of ENS are still unknown. In this study, we aimed to clarify the expression and neurochemical characterization of HAP1 in the submucosal plexuses of the small intestine in adult mice and rats. HAP1 was highly expressed in the submucosal plexuses of both rodents. The percentage of HAP1-immunoreactive submucosal neurons was not significantly varied between the intestinal segments of these rodents. Double immunofluorescence results revealed that almost all the cholinergic secretomotor neurons containing ChAT/ CGRP/ somatostatin/ calretinin, non-cholinergic secretomotor neurons containing VIP/NOS/TH/calretinin, and vasodilator neurons containing VIP/calretinin expressed HAP1. Our current study is the first to clarify that STB/HAP1 is expressed in secretomotor and vasodilator neurons of submucosal plexuses, suggesting that STB/HAP1 might modulate or protect the secretomotor and vasodilator functions of submucosal neurons in ENS., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Ltd and Japan Neuroscience Society. All rights reserved.)

In Asian developing countries, undeveloped and ineffective sewer systems are causing surface water pollution by a lot of contaminants, especially pharmaceuticals and personal care products (PPCPs). Therefore, the risks for freshwater fauna need to be assessed. The present study aimed at: i) elucidating the contamination status; ii) evaluating the bioaccumulation; and iii) assessing the potential risks of PPCP residues in surface water and freshwater fish from three Asian countries. We measured 43 PPCPs in the plasma of several fish species as well as ambient water samples collected from India (Chennai and Bengaluru), Indonesia (Jakarta and Tangerang), and Vietnam (Hanoi and Hoa Binh). In addition, the validity of the existing fish blood-water partitioning model based solely on the lipophilicity of chemicals is assessed for ionizable and readily metabolizable PPCPs. When comparing bioaccumulation factors calculated from the PPCP concentrations measured in the fish and water (BAF measured ) with bioconcentration factors predicted from their pH-dependent octanol-water partition coefficient (BCF predicted ), close values (within an order of magnitude) were observed for 58-91 % of the detected compounds. Nevertheless, up to 110 times higher plasma BAF measured than the BCF predicted were found for the antihistamine chlorpheniramine in tilapia but not in other fish species. The plasma BAF measured values of the compound were significantly different in the three fish species (tilapia > carp > catfish), possibly due to species-specific differences in toxicokinetics (e.g., plasma protein binding and hepatic metabolism). Results of potential risk evaluation based on the PPCP concentrations measured in the fish plasma suggested that chlorpheniramine, triclosan, haloperidol, triclocarban, diclofenac, and diphenhydramine can pose potential adverse effects on wild fish. Results of potential risk evaluation based on the PPCP concentrations measured in the surface water indicated high ecological risks of carbamazepine, sulfamethoxazole, erythromycin, and triclosan on Asian freshwater ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Complex multi-organ interactions such as coexistence of hepato-renal dysfunction in heart failure (HF) adversely affects patient prognosis. However, the association between liver/kidney dysfunction and frailty and effects of their coexistence on HF prognosis remain unclear., Methods: This retrospective cohort study included 922 patients with HF (median age, 72 years; interquartile range: 62-79 years). All patients underwent hepato-renal function testing using the model for end-stage liver disease, excluding international normalized ratio (MELD-XI) score and frailty score. Frailty was measured using a composite of four markers: handgrip strength, gait speed, serum albumin, and activities of daily living status, combined into a total frailty score (range 0-12). Patients were assigned to a frailty score <5 (without frailty) or ≥5 (frailty) group. The multivariable logistic regression model was used to analyze the association between MELD-XI score and frailty; the prognostic value of high MELD-XI score and frailty coexistence was investigated. The endpoint was all-cause mortality., Results: After adjusting for covariates and dividing by the median MELD-XI score, the high MELD-XI score group [odds ratio: 1.663, 95 % confidence interval (CI): 1.200-2.304, p = 0.002] was significantly associated with frailty, compared with the low MELD-XI score group. One hundred and fifty deaths occurred during follow-up (median, 2.13 years; interquartile range, 0.93-4.09 years). Patients in the high MELD-XI score/frailty group had a significantly higher mortality risk, even after adjusting for HF severity (hazard ratio: 4.326, 95 % CI: 2.527-7.403, p < 0.001)., Conclusions: Hepato-renal dysfunction is associated with frailty in patients with HF, which affects patient prognosis., Brief Summary: This study showed that hepato-renal dysfunction in patients with HF, as assessed by the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score, is associated with frailty, even after adjusting for factors involved in the frailty or severity of HF. Additionally, high MELD-XI score combined with frailty is associated with a poorer prognosis. These results suggest that hepato-renal dysfunction and frailty can be used for risk stratification in patients with HF., Competing Interests: Declaration of competing interest The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: To compare the Fried criteria for frailty diagnosis with the Frailty Screening Index (FSI) and the fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) scale in older patients with cardiovascular disease (CVD)., Design: We conducted a retrospective 1-year follow-up cohort study of adult inpatients who participated in a cardiac rehabilitation program between June 2016 and September 2018., Setting and Participants: We included 1472 Japanese patients age 65 years and older with CVD. After excluding 765 patients with incomplete frailty measurements, 707 patients were included in the analysis., Methods: Frailty and physical function were measured before hospital discharge according to each of the 3 definitions. Outcomes were all-cause mortality and physical dysfunction., Results: The prevalence of frailty according to the Fried criteria, the FRAIL scale, and the FSI was 213 (30.1%), 181 (25.6%), and 186 (26.3%), respectively. The FSI and the FRAIL scale showed moderate agreement with the Fried criteria [vs FSI: K = 0.52, 95% confidence interval (CI): 0.45-0.59; vs FRAIL scale: K = 0.45, 95% CI: 0.37-0.52; all P < .001]. We found a significant correlation between all-cause mortality and frailty assessed by all of the definitions, even after multivariate adjustment [FSI: hazard ratio (HR): 2.43, 95% CI: 1.30-4.58, P = .006; FRAIL scale: HR: 2.32, 95% CI: 1.21-4.45, P = .011; Fried criteria: HR: 1.99, 95% CI: 1.04-3.82, P = .038). However, the prediction accuracy of the FRAIL scale was higher than that of the FSI and comparable to that of the Fried criteria for physical dysfunction., Conclusions and Implications: The FSI and the FRAIL scale showed moderate agreement with the Fried criteria regarding frailty diagnostic performance and had comparable prognostic value. However, only the FRAIL scale was as accurate as the Fried criteria in screening for physical dysfunction., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: No reports explicitly examined the relationship between work defined as a certain type of social participation or role and the protective effect on the prognosis of patients with heart failure (HF) by preventing frailty. Therefore, this study examined whether social participation through work before admission relates to future adverse events in HF patients aged ≥65 years, and whether each frailty domain mediates the association between work and prognosis as a second analysis of a multi-centered prospective study (FRAGILE-HF study)., Methods: We retrospectively reviewed 1,332 older patients with HF whose work status before admission to the hospital were investigated. We assessed the physical, cognitive, and social domains of frailty and performed causal mediation analysis to examine the mediating relationship of each frail domain between work status before admission and 1-year combined events (HF-related readmission and all-cause death)., Results: The subjects' median age was 81 years, and 56.9% (758/1,332) were male. Among the three domains of frailty, work before admission reduced only social frailty after adjusting for confounding factors (odds ratio: 0.505, 95% confidence interval: 0.364-0.701). Patients with work before admission had a significantly better prognosis (hazard ratio: 0.720, 95% confidence interval: 0.523-0.989). Only social frailty partly mediated the relationship between work status and combined events (p <0.05)., Conclusions: Work status before admission is associated with 1-year combined events, in part through social frailty., (Copyright © 2021. Published by Elsevier Ltd.)

To develop antimicrobial restorative materials for root caries, we assessed a 4-META/MMA-TBB resin (Bondfill SB Plus, Sun Medical) containing benzalkonium chloride (BAC) or cetylpyridinium chloride (CPC) at 1.25, 2.5, and 5.0 wt%. The same resin without antibacterial agent was used as control. The degree of conversion was measured by attenuated total reflectance-Fourier transform infrared spectroscopy. The 3-point flexural strength test was conducted according to ISO 4049. The antimicrobial effect against three oral bacteria (Streptococcus mutans, S. sobrinus, and Actinomyces naeslundii) was assessed using agar diffusion tests. The shear bond strength to root dentin was assessed after 24 h of storage in water with or without 10,000 thermal cycles. The shear bond strength data were statistically compared using a linear mixed-effects model (α = 0.05). The specimen with 5.0 wt% BAC showed a significantly higher degree of conversion than the control, but it also had significantly lower flexural strength and lower shear bond strength after thermal cycling than the other specimens. When BAC or CPC was added at ≥ 2.5 wt%, the resins inhibited the growth of the three investigated microbes. In conclusion, both BAC and CPC showed significant antimicrobial effects when added at 5.0 wt% to the 4-META/MMA-TBB resin. Up to 2.5 wt%, neither antimicrobial agent affected the degree of conversion, flexural strength, or shear bond strength of the resin., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: We investigated whether the FRAIL scale questionnaire is consistent with the Fried criteria, predicts all-cause mortality, and reflects physical dysfunction in patients with heart failure (HF)., Design: Secondary analysis of FRAGILE-HF, a cohort study that enrolled participants from 2016 to 2018 and followed-up for 1-year of discharge., Setting and Participants: A prospective multicenter cohort study in which 15 hospitals in Japan (8 university hospitals and 7 nonuniversity teaching hospitals) participated. We prospectively enrolled 1332 consecutive hospitalized patients ≥65 years old with HF and analyzed 1028 patients after excluding 304 patients with missing data on the FRAIL scale., Methods: The FRAIL scale, the Fried model, and physical function were measured before discharge. The endpoint was all-cause mortality., Results: According to the FRAIL scale, 459 (44.6%) and 491 (47.8%) were classified as frail and prefrail, respectively. The Kappa coefficient between the FRAIL scale and the Fried criteria were 0.39 [95% confidence interval (CI) 0.34-0.44; P < .001]. The area under the receiver-operating characteristic curves for frailty diagnosed by the Fried criteria of the FRAIL scale was 0.74 (95% CI 0.71-0.76; P < .001). A total of 118 deaths occurred during 1 year of follow-up. After adjusting for the MAGGIC risk score and log-BNP, The FRAIL scale predicted all-cause mortality (hazard ratio 1.17; 95% CI 1.01-1.36; P = .035). The FRAIL scale was also associated with various physical dysfunctions that correlated with poor prognosis., Conclusions and Implications: The FRAIL scale had moderate consistency with the Fried criteria, predicted all-cause mortality, and reflected clinically important physical dysfunctions., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Although oxygen uptake (VO 2 ) during exercise stress is a surrogate marker for prognosis in patients with cardiovascular disease (CVD), the stress test is sometimes difficult to perform owing to patient conditions, such as ageing or comorbidities. We investigated the relationships between VO 2 during usual gait with physical function and prognosis in patients with CVD., Methods: This single-centre observational study enrolled consecutive patients who were hospitalized for CVD treatment. Isometric quadriceps strength (QS) and 6-min walk distance (6MWD) as physical functions, and VO 2 during usual gait speed were measured at hospital discharge. We assessed the changes in VO 2 per body weight between at rest and during gait divided by gait speed (VO 2 /kg/gait) and analysed the relationships of VO 2 /kg/gait with physical functions and composite incidences of all-cause death or unplanned readmission after discharge., Results: In 367 patients (age, 65 ± 13 years; females, 34%), 112 clinical events occurred. VO 2 /kg/gait showed significant negative correlations to QS (β = -0.114, p = 0.024) and 6MWD (β = -0.163, p < 0.001) after adjusting for confounding factors. High VO 2 /kg/gait was significantly associated with a high rate of clinical events (hazard ratio for 1 standard deviation of VO 2 /kg/gait, 1.36; 95% confidence interval, 1.11-1.66). This association was also observed in subgroups of older age and frailty., Conclusions: High VO 2 during usual gait was a relevant factor for low physical function and poor prognosis in patients with CVD and even in older age and frailty, meaning that VO 2 during usual gait might be a novel and useful marker in clinical practice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Although muscle dysfunctions are widely known as a poor prognostic factor in patients with cardiovascular disease, no study has examined whether the addition of low skeletal muscle density (SMD) assessed by computed tomography (CT) to muscle dysfunctions is useful. This study examined whether SMDs can strengthen the predictive ability of muscle dysfunctions for adverse events in patients who underwent cardiovascular surgery., Methods and Results: We retrospectively reviewed 853 patients aged ≥40 years who had preoperative CT for risk management purposes and who measured muscle dysfunctions (weakness: low grip strength and slowness: slow gait speed). Low SMD based on transverse abdominal CT images was defined as a mean Hounsfield unit of the psoas muscle <45. All definitions of muscle dysfunction (weakness only, slowness only, weakness or slowness, weakness and slowness), the addition of SMDs was shown to significantly improve the continuous net reclassification improvement and integrated discrimination improvement for adverse events in all analyses (p < 0.05). Low SMDs combined with each definition of muscle dysfunction had the highest risk of all-cause death (hazard ratio: lowest 3.666 to highest 6.002), and patients with neither low SMDs nor muscle dysfunction had the lowest risk of all-cause and cardiovascular-related events., Conclusion: The addition of SMDs consistently increased the predictive ability of muscle dysfunctions for adverse events. Our results suggest that when CT is performed for any clinical investigation, the addition of the organic assessment of skeletal muscle can strengthen the diagnostic accuracy of muscle wasting., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Dynapenia, defined as age-associated loss of skeletal muscle strength, is associated with increased mortality rate, poor activities of daily living, and reduced quality of life. Therefore, dynapenia appears to be a better independent predictor of mortality than sarcopenia in the elderly. However, the prognostic utility of dynapenia in patients with cardiovascular disease (CVD) is not clear. This study was performed to examine the prognostic utility of dynapenia defined by the criteria of Manini et al. in patients with CVD., Methods: The findings of 4192 consecutive patients ≥30 years old (median [interquartile range (IQR)] age 69 [60-76] years, 2874 males) with CVD were reviewed. Grip strength and quadriceps isometric strength (QIS) were measured just before hospital discharge, and low grip strength (<26 kg in males and <18 kg in females), low QIS (<45.0% body mass [BM] and <35.0% BM in males and females, respectively) were considered to indicate dynapenia. The endpoint was all-cause mortality., Results: A total of 507 deaths occurred during follow-up (median 2.0 years, IQR 0.8-4.4 years). The overall prevalence of dynapenia was 33.6% and increased with age (p for trend < 0.01). Females showed a significantly higher prevalence rate of dynapenia than males (43.3% vs. 29.2%, respectively; p < 0.01). Patients with dynapenia showed higher all-cause mortality rate than non-dynapenia patients (adjusted hazard ratio: 1.84; 95% confidence interval: 1.51-2.23; p < 0.01)., Conclusions: Dynapenia has a high prevalence among patients with CVD and is associated with increased mortality rate., Competing Interests: Conflict of interest The authors declare there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The pregnane X receptor (PXR) is one of the major transcription factors that regulate the expression of different drug-metabolizing enzymes and transporters. Adenosine-to-inosine RNA editing, the most frequent nucleotide conversion on RNA, which is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, may modulate gene expression and function. Here, we investigated the potential regulation of human PXR expression by adenosine-to-inosine RNA editing. Knockdown of ADAR1 increased PXR mRNA level, and the knockdown of ADAR1 or ADAR2 significantly increased PXR protein level in HepaRG cells. In HepG2 cells, the knockdown of ADAR1 or ADAR2 significantly increased PXR mRNA and protein levels. The increase in the PXR protein by ADAR1 knockdown resulted in increased cytochrome P450 3A4 (CYP3A4) transactivity and CYP3A4 and UDP-glucuronosyltransferase 1A1 (UGT1A1) expression. A reporter assay revealed that the 3'-untranslated region (UTR) of PXR mRNA, especially from +3371 to +3440, is responsible for the ADAR-mediated post-transcriptional control of PXR expression, despite the lack of RNA edited sites in this region. Collectively, we found that PXR is negatively regulated by ADAR1 via an indirect mechanism, which facilitates the degradation of PXR mRNA. We could demonstrate that ADAR1 can cause interindividual variability in hepatic drug metabolism potencies., Competing Interests: Declaration of competing interest Authors have no competing interest to declare., (Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Background: This study was performed to test the hypothesis that low quadriceps isometric strength (QIS) is associated with greater risk of mortality and has the additive prognostic significance to the severity of heart failure (HF) and gait speed in older patients with HF., Methods: A retrospective cohort study was performed in 1273 patients ≥ 60 years of age with HF (mean age 75 ± 8 years, 59.1% men); all of whom were evaluated during hospitalization for usual gait speed and maximal QIS. The QIS was expressed relative to body mass (% BM). The endpoint was all-cause mortality., Results: Over a median follow-up period of 1.59 years (interquartile range, 0.58 to 3.42 years), 224 patients died. The cutoff value based on the Youden index for the QIS discriminating those at high risk of mortality was 36.2% BM for overall, and we defined less than this cutoff point of QIS as low QIS. After adjustment for the HF risk score, the hazard ratio in low QIS was 1.55 for overall (95% confidence interval [CI], 1.17-2.06). The addition of low QIS to the HF risk score and gait speed was associated with significant increases in both net reclassification improvement (NRI, 0.239 for overall; 95% CI, 0.096-0.381) and integrated discrimination improvement (IDI, 0.004 for overall; 95% CI, 0.001-0.009) for all-cause mortality., Conclusion: Low QIS was strongly associated with poor prognosis and showed complementary prognostic predictive capability to the HF risk score and gait speed in older patients with HF., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to assess the influence of alumina sandblasting on the flexural strength of the latest generation of highly translucent yttria partially stabilized dental zirconia (Y-PSZ). Fully-sintered zirconia disk-shaped specimens (14.5-mm diameter; 1.2-mm thickness) of four Y-PSZ zirconia grades (KATANA HT, KATANA STML, KATANA UTML, all Kuraray Noritake; and Zpex Smile, Tosoh) were sandblasted at 0.2 MPa with 50-μm alumina (Al 2 O 3 ) sand (Kulzer) or left as-sintered (control). For each zirconia grade, the yttria (Y 2 O 3 ) content was determined using X-ray fluorescence (XRF). Surface roughness was assessed using 3D confocal laser microscopy. Micro-Raman spectroscopy (μ-Raman) and X-ray diffraction (XRD) were used to assess potentially induced residual stresses. Biaxial flexural strength (n = 20) was statistically compared by Weibull analysis. Focused ion beam - scanning electron microscopy (FIB/SEM) was used to observe the subsurface microstructure. Fracture surfaces after biaxial flexural strength testing were observed by SEM. KATANA UTML had the highest Y 2 O 3 content (6 mol%), followed by KATANA STML and Zpex Smile (5 mol%), and KATANA HT (4 mol%). Al 2 O 3 -sandblasting significantly increased surface roughness of KATANA UTML and Zpex Smile. μRaman and XRD revealed the presence of residual compressive stress on all Al 2 O 3 -sandblasted surfaces. FIB/SEM revealed several sub-surface microcracks in the sandblasted specimens. Weibull analysis revealed that Al 2 O 3 -sandblasting increased the characteristic strength of KATANA HT, KATANA STML, whereas it decreased the strength of KATANA UTML. The strength enhancement after Al 2 O 3 -sandblasting of KATANA HT was the highest, followed by KATANA STML. For Zpex Smile, the influence was statistically insignificant. The impact of Al 2 O 3 -sandblasting on the Weibull modulus was controversial. The strength of zirconia after Al 2 O 3 -sandblasting is determined by the balance between microcrack formation (decreased strength) and surface compressive stress build-up (increased strength)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background & Aims: The Global Leadership Initiative on Malnutrition (GLIM) published a new international standard for defining malnutrition in 2018. The GLIM criteria were compared with the European Society for Clinical Nutrition and Metabolism (ESPEN) criteria in relation to physical function and mortality risk in patients with cardiovascular disease (CVD)., Methods: A total of 921 CVD patients ≥ 20 years old (67.8 ± 13.4 years, 631 men) hospitalised for heart failure, acute coronary syndrome and other conditions were stratified according to the presence or absence of malnutrition according to the GLIM and ESPEN criteria. Physical function was assessed by measuring grip strength, 6-minute walking distance and quadriceps isometric strength before hospital discharge, and the endpoint was all-cause mortality., Results: During the median follow-up period of 2.3 years (interquartile range, 0.9-3.5 years), 194 deaths occurred in the study population. Malnutrition defined by the GLIM criteria was significantly associated with low physical function. Malnutrition defined by both the GLIM and ESPEN criteria was significantly related to all-cause mortality (P < 0.05)., Conclusions: Malnutrition defined according to the GLIM criteria was a predictor of both low physical function and mortality in patients with CVD., Competing Interests: Conflicts of interest The authors declare there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems has raised concern about their potential adverse effects on aquatic organisms. Considering the fact that the physiological/biological effects of PPCPs are triggered when their concentrations in the organism exceeds the respective threshold values, it is important to understand the bioconcentration and toxicokinetics of PPCPs in aquatic organisms. In the present study, we developed a convenient analytical method for the determination of 65 pharmaceuticals and 7 personal care products (log K ow  = 0.14-6.04) in plasma and whole-body tissues of fish. The analytical method consists of ultrasound-assisted extraction in methanol/acetonitrile (1:1, v/v,) acidified with acetic acid-ammonium acetate buffer (pH 4), cleanup on a HybridSPE®-Phospholipid cartridge (zirconia-coated silica cartridge), and quantification with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Acceptable accuracy (internal standard-corrected recovery: 70%-120%) and intra- and inter-day precision (coefficient of variation: <15%) were obtained for both plasma and whole-body tissue samples. In addition, low method detection limits were achieved for both plasma (0.0077 to 0.93 ng mL -1 ) and whole-body tissue (0.022 to 4.3 ng g  -   1 wet weight), although the developed method is simple and fast - a batch of 24 samples can be prepared within 6 h, excluding the time for measurement with LC-MS/MS. The developed method was successfully applied to the analysis of PPCPs in plasma and whole-body tissue samples of fish collected in a treated wastewater-dominated stream, for a comprehensive evaluation of their bioconcentration properties. The analytical method developed in the present study is sufficiently accurate, sensitive, and rapid, and thus highly useful for the comprehensive evaluation of PPCP residues in fish and would aid in future exposome and risk assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: The early prediction of frailty at discharge in elderly patients hospitalized with heart failure (HF) is essential for clinical management and therapeutic decision-making. This study was performed to examine whether the rising time from bed measured immediately after admission can be used as a predictor of frailty in these patients., Methods: A retrospective cohort study was performed in a population of 387 consecutive elderly patients with HF. Rising time from bed was measured within 2 days after admission when cardiac rehabilitation was started. Frailty was assessed at hospital discharge using a composite of four markers as a frailty score (range, 0-12): gait speed, handgrip strength, serum albumin, and activities of daily living status. The patients were divided into two groups based on frailty score <5 (non-frail) or ≥5 (frail)., Results: The study population had a mean age of 75 years and 63.6 % were men. The median rising time was 6.8s, and 53.5 % were classified as frail. After adjustment for various factors, rising time was independently associated with frailty (odds ratio=1.10; 95 % confidence index=1.04-1.18). The area under the receiver operating characteristics curve of rising time for frailty was 0.71, and the cut-off value for rising time to identify those at high risk of frailty was 7.1s., Conclusions: Rising time from bed measured within 2 days after admission was shown to be an independent predictor of frailty at hospital discharge in elderly patients hospitalized for HF., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Introduction: Although early intervention for chronic kidney disease (CKD) and renal anemia are desirable, these conditions are often asymptomatic during their early stages and may be underdiagnosed., Methods: We retrospectively analyzed Japanese administrative claims data for general and hospital populations. The data period for the general and hospital data ranged from January 2011 to December 2016 and from April 2008 to July 2017, respectively. CKD stage was determined by estimated glomerular filtration rate (eGFR). Anemia was defined per Japanese guidelines using hemoglobin (Hb) values. The proportion of patients who had eGFR-defined stages G3-G5 CKD without a CKD diagnosis, and Hb-defined anemia without an anemia diagnosis or treatment records, was estimated., Results: Among 16,779 (general) and 68,161 (hospital) patients, a high proportion of G3 CKD patients did not have a CKD-related diagnosis (general: G3a, 95.0%; G3b, 68.4%; hospital: G3a, 89.2%; G3b, 67.9%); however, some patients were treated with antihypertensives. Among anemic patients, 75.7% (G3a) and 66.7% (G3b) of the general population, and 56.2% (G3a) and 47.5% (G3b) of the hospital population, did not have an anemia-related diagnosis or treatment. CKD and anemia were more likely to be diagnosed in patients with G4 and G5 CKD., Conclusion: A high proportion of G3 CKD patients did not have a CKD-related diagnosis. Likewise, many anemic patients with G3 CKD did not have an anemia-related diagnosis. Despite the lack of a CKD-related diagnosis, some patients received appropriate treatment (e.g., antihypertensives). Further outreach to CKD and anemia patients at earlier stages may be warranted., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Background: Although respiratory muscle weakness (RMW) is known to predict prognosis in patients with heart failure with reduced ejection fraction (HFrEF), RMW prevalence and its prognosis in those with preserved ejection fraction (HFpEF) remain unknown. We aimed to investigate whether the RMW predicted mortality in HFpEF patients., Methods: We conducted a single-centre observational study with consecutive 1023 heart failure patients (445 in HFrEF and 578 in HFpEF). Maximal inspiratory pressure (PI max ) was measured to assess respiratory muscle strength at hospital discharge, and RMW was defined as PI max <70% of predicted value. Endpoint was all-cause mortality after hospital discharge, and we examined the influence of RMW on the endpoint., Results: Over a median follow-up of 1.8 years, 134 patients (13.1%) died; of these 53 (11.9%) were in HFrEF and 81 (14.0%) in HFpEF. RMW was evident in 190 (42.7%) HFrEF and 226 (39.1%) HFpEF patients and was independently associated with all-cause mortality in both HFrEF (adjusted hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.17-3.88) and HFpEF (adjusted HR: 2.85, 95% CI: 1.74-4.67) patients. Adding RMW to the multivariate logistic regression model significantly increased area under the receiver-operating characteristic curve (AUC) for all-cause mortality in HFpEF (AUC including RMW: 0.78, not including RMW: 0.74, P = 0.026) but not in HFrEF (AUC including RMW: 0.84, not including RMW: 0.82, P = 0.132)., Conclusions: RMW was observed in 39% of HFpEF patients, which was independently associated with poor prognosis. The additive effect of RMW on prognosis was detected only in HFpEF but not in HFrEF., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Sarcopenic obesity is a health condition involving a combination of excess adipose tissue and loss of muscle mass. Although sarcopenic obesity is known to contribute to the morbidity and mortality of chronic diseases, limited data are available in patients with cardiovascular disease. The present study was performed to examine whether sarcopenic obesity determined by preoperative computed tomography (CT) is a useful predictor of postoperative mortality in patients undergoing cardiovascular surgery., Methods: We reviewed the findings in 664 consecutive cardiovascular surgery patients (mean age, 65.8±12.7 years; male, 66.6%) who underwent preoperative CT including the level of the third lumbar vertebra for clinical purposes. Psoas muscle attenuation (MA) and visceral adipose tissue (VAT) were measured as metrics of sarcopenia and obesity, respectively. Sarcopenia was defined as low MA (below median), while obesity was defined as high VAT (≥103cm 2 for males and ≥69cm 2 for females). The endpoint was all-cause mortality and secondary outcomes were muscle function., Results: After adjusting for age and sex, sarcopenic obesity showed significant associations with lower grip strength and quadriceps strength, slower gait speed, and shorter 6-min walking distance compared to the normal group (p<0.05). On multivariate Cox regression analysis, sarcopenic obesity was associated with increased risk of mortality after adjusting for EuroSCORE (hazard ratio, 3.04; 95% confidence interval, 1.25-7.40)., Conclusions: Sarcopenic obesity is associated with poor muscle function and all-cause mortality in patients undergoing cardiovascular surgery., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: Arm circumference (AC) and nutritional screening tools have been shown to have prognostic capability in patients with cardiovascular disease (CVD). This study aimed to compare the prognostic predictive capabilities of AC and nutritional screening tools in older patients with CVD., Methods and Results: The study population consisted of 949 admitted patients ≥60 years old with CVD. Patients underwent AC measurement and nutritional screening before hospital discharge. We used the controlling nutritional status index (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) as nutritional screening tools. The end point of the study was all-cause mortality. The mean age of the study population was 72.3 ± 7.2 years, and 68.2% of the patients were male. A total of 130 deaths occurred over a median follow-up period of 2.2 years (interquartile range, 1.1-3.8 years). After adjusting for other prognostic factors, AC (hazard ratio [HR]: 0.59; p < 0.001), CONUT (HR: 0.82; p = 0.016), GNRI (HR: 0.77; p = 0.040), and PNI (HR: 0.80; p = 0.014) were significant predictors of mortality. However, adding AC to the multivariate-adjusted model (0.739 vs. 0.714, respectively; p = 0.037), but not CONUT, GNRI, or PNI (0.724, 0.717, and 0.723 vs. 0.714; p = 0.072, p = 0.306, and p = 0.127, respectively), significantly increased the area under the curve on receiver operating characteristic curve., Conclusions: AC, but not nutritional screening tools, plays a complementary role to preexisting prognostic factors for predicting prognosis in older patients with CVD., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Epithelioid glioblastoma, a high-grade, diffuse astrocytic tumor variant, comprises closely packed epithelioid cells and rhabdoid cells. This rare tumor usually develops in the cerebral cortex and diencephalon; however, in the case reported here, it was located intraventricularly., Case Description: A 47-year-old woman was referred to our hospital with a right intraventricular mass that had rapidly increased in size. On discovery of the tumor 3 years earlier at the referring hospital, the mass was small, calcified, and attached to the periventricular parenchyma. Over the next 2 years, the mass grew slowly, as observed on periodic magnetic resonance imaging scans. Forty days before the referral, the patient experienced headache and nausea, and marked growth and intratumoral hemorrhage were visible on a computed tomography scan of the head. The tumor was partially removed via a superior parietal lobule corticotomy. Histopathological examination confirmed an isocitrate dehydrogenase-wild-type epithelioid glioblastoma with a BRAF V600E mutation, but the original slow-growing lesion was no longer detected. Consequently, we assume that in this case, a low-grade glioma transformed into an aggressively malignant epithelioid glioblastoma., Conclusions: We present the first case of an intraventricular epithelioid glioblastoma that might have arisen from a low-grade glioma with calcification. We recommend including this tumor variant in the differential diagnosis of lateral ventricle tumors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Low skeletal muscle density, determined using computed tomography (CT), has yet to be examined in terms of muscle function and prognostic capability in patients who require open cardiovascular surgery. This study was performed to examine whether psoas muscle area and density, determined using CT, are associated with postoperative mortality in patients who undergo cardiovascular surgery., Methods: We reviewed the findings in 773 consecutive patients who underwent preoperative CT imaging, including the level of the third lumbar vertebra for clinical purposes. We measured grip strength, gait speed, and 6-minute walking distance to assess muscle function before hospital discharge. Skeletal muscle area was calculated from psoas muscle cross-sectional area (in squared centimeters) on preoperative CT images at the level of the third lumbar vertebra divided by the square of the patient's height in metres to give the skeletal muscle index (SMI). Skeletal muscle density determined by muscle attenuation (MA) was calculated by measuring the average Hounsfield units of the psoas muscle cross-sectional area., Results: The mean age of the study population was 65.0 ± 13.1 years, and 64.7% of the patients were male. Multivariate logistic regression analysis and multivariate Cox regression analysis showed that low MA, but not SMI, was significantly associated with muscle function, and all-cause mortality (P < 0.05). Kaplan-Meier analysis showed that low MA, but not low SMI, predicted mortality (P = 0.014)., Conclusions: Low skeletal muscle density, but not skeletal muscle area, predicted poorer muscle function and mortality in patients who undergo cardiac surgery., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Bacterial adhesion to dental materials is a major cause of caries and periodontitis, necessitating the development of compounds such as yttria-stabilized zirconia (YSZ) and silver nanoparticles (AgNPs), which are widely employed in medicine due to their high antimicrobial activity and low cytotoxicity. The main goal of this study is the synthesis of the broad antimicrobial activity of AgNP-coated YSZ with facile methods. The bactericidal AgNPs were immobilized on the surface of YSZ and tested for bactericidal activity against Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Aggregatibacter actinomycetemcomitans based on ISO 22196:2007. The loading of AgNPs was optimized by culturing mouse fibroblast cells on AgNP-coated YSZ with cell viability test based on ISO 10993-5. In addition, the silver release profile of AgNP-coated YSZ in artificial saliva was determined using an accelerated aging test. Antibacterial activity, and cell viability test revealed optimum performance with no cytotoxicity at a level of 32 μg/cm 2 . Accelerated aging test showed that the AgNP-coated surface was extremely stable, exhibiting a total silver leaching level of only 1% and confirming the effectiveness of this coating method for retaining AgNPs while exerting an antibacterial effect against oral pathogens. This finding also implies that the bactericidal action of AgNP-coated YSZ is not mediated by the released Ag ions, but rather corresponds to contact killing., Abbreviations: Yttria-stabilized zirconia, YSZ; silver nanoparticles, AgNPs; field emission scanning electron microscopy, FE-SEM; X-ray photoelectron spectroscopy, XPS; grazing incidence X-ray diffraction, GIXRD; ultraviolet-visible, UV-vis; inductively coupled plasma atomic emission spectrometry, ICP-AES., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: A simple and inexpensive tool for screening of sarcopenia would be helpful for clinicians. The present study was performed to determine whether the SARC-F questionnaire is useful in screening of patients with cardiovascular disease (CVD) for impaired physical function., Design: Cross-sectional study., Setting: Single university hospital., Participants: A total of 235 Japanese patients ≥65 years old admitted to our hospital for CVD., Measurements: SARC-F, handgrip strength, leg strength, respiratory muscle strength, standing balance, usual gait speed, Short Physical Performance Battery (SPPB) score, and 6-minute walking distance were measured before discharge from hospital. The patients were divided into 2 groups according to SARC-F score: SARC-F < 4 (nonsarcopenia group) and SARC-F ≥ 4 (sarcopenia group)., Results: The sarcopenia prevalence rate was 25.5% and increased with age (P trend < .001). The sarcopenia group (SARC-F score ≥ 4) had significantly lower handgrip strength, leg strength, and respiratory muscle strength, poorer standing balance, slower usual gait speed, lower SPPB score, and shorter 6-minute walking distance compared to the nonsarcopenia group (SARC-F score < 4). Patients in the sarcopenia group had consistently poorer physical function even after adjusting for covariates., Conclusion: The SARC-F questionnaire is a useful screening tool for impaired physical function in elderly CVD patients. These findings support the use of the SARC-F for screening in hospital settings., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Measurement of the ankle brachial index (ABI) is a simple, noninvasive means of diagnosing peripheral arterial disease, and has been shown to be associated with mortality rate. Here, we examined the association between ABI and physical function in patients with heart failure (HF)., Methods: The study population consisted of 524 admitted patients (67.2±13.9years, 343 males) with HF. Blood pressure and the ABI were determined by oscillometry. Prior to hospital discharge, ABI, 6-minute walking distance, walking velocity, handgrip strength, quadriceps isometric strength, and standing balance were determined. The 524 patients were divided according to ABI as follows: ABI≤0.90 (low ABI), ABI 0.91 to 0.99 (borderline ABI), and ABI 1.00 to 1.40 (normal ABI)., Results: Lower ABI values were associated with shorter 6-minute walking distance (p trend=0.001), slower walking velocity (p trend=0.023), and poorer standing balance (p trend=0.048). There were no significant associations between ABI and handgrip strength or quadriceps isometric strength. After adjusting for potential confounders, patients with ABI≤0.90 had shorter 6-minute walking distance compared to those with ABI 1.00 to 1.40 (adjusted mean value: 344m vs. 395m, respectively, p<0.001). There were no significant differences in any of the other physical function parameters examined., Conclusions: In patients with HF, low ABI is associated with the magnitude of impairment in walking endurance., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study was performed to investigate the complementary role of arm circumference to body mass index (BMI) in risk stratification of patients with heart failure (HF)., Background: High BMI is associated with improved survival in patients with HF. However, it does not discriminate between fat and lean muscle as a predominant factor., Methods: BMI, waist circumference (WC), and mid-upper arm circumference (MUAC) were evaluated in 570 consecutive Japanese patients with HF (mean age 67.4 ± 14.0 years). Patients were stratified into low and high groups according to BMI, WC, and MUAC and combined into low- or high-BMI and low- or high-WC groups or low- or high-BMI and low- or high-MUAC groups. The endpoint was all-cause mortality., Results: Seventy deaths occurred over a median follow-up period of 1.5 years (interquartile range: 0.7 to 2.8 years). After adjusting for several pre-existing prognostic factors, including Seattle Heart Failure Score and exercise capacity, BMI (hazard ratio [HR]: 0.68; p = 0.016), WC (HR: 0.76; p = 0.044), and MUAC (HR: 0.52; p < 0.001) were all inversely associated with prognosis. Compared with the high-BMI/high-WC group, both the low-BMI/high-WC and low-BMI/low-WC groups showed comparably poorer prognosis. However, the low-BMI/low-MUAC group but not the low-BMI/high-MUAC group showed poorer prognosis than the high-BMI/high-MUAC group. Adding MUAC to BMI (0.70 vs. 0.63, p = 0.012) but not WC to BMI (0.64 vs. 0.63, p = 0.763) significantly increased the area under the curve on receiver-operating characteristic curve analysis., Conclusions: MUAC, but not WC, plays a complementary role to BMI in predicting prognosis in patients with HF., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)