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Background Bariatric surgery is an effective treatment for severe obesity and its associated medical problems. Preoperative factors that predict postoperative weight loss remain to be fully characterized, however. Methods Anthropometric and laboratory data were collected retrospectively for severely obese patients who underwent laparoscopic sleeve gastrectomy (LSG) between April 2016 and July 2019 at our hospital. Preoperative factors that predicted weight loss at 1 year after LSG were investigated. Results A total of 122 subjects (45 men and 77 women) underwent LSG. The mean ± SD age and body mass index at surgery were 44.4 ± 10.4 years and 40.7 ± 6.7 kg/m2. The percent total weight loss (%TWL) was 27.0 ± 8.6 among all subjects, 26.4 ± 8.0 among men, and 27.4 ± 8.9 among women, with no significant difference between the sexes. The %TWL showed a significant inverse correlation with serum cortisol level in men and with age and the visceral/subcutaneous fat area ratio in women. Multivariable regression analysis revealed the presence of type 2 diabetes and the serum cortisol concentration to be negatively associated with %TWL among all subjects and men, respectively. Receiver operating characteristic curve analysis identified an optimal cutoff of 10 µg/dL for prediction of a %TWL of ≥ 25 in men by serum cortisol level. Conclusions Serum cortisol concentration was identified as a predictor for postoperative weight loss in men. Our results may thus help inform the decision to perform LSG or more effective surgical procedures in men with severe obesity. Graphical Abstract

This study aimed to clarify associations between neuropsychological scales and regional cerebral blood flow (rCBF) of on ‍

Mutations in optineurin (OPTN) have been identified in a small proportion of sporadic and familial amyotrophic lateral sclerosis (ALS) cases. Recent evidences suggest that OPTN would be involved in not only the pathophysiological mechanisms of motor neuron death of ALS but also myofiber degeneration of sporadic inclusion body myositis. However, the detailed role of OPTN in muscle remains unclear. Initially, we showed that OPTN expression levels were significantly increased in the denervated muscles of mice, suggesting that OPTN may be involved in muscle homeostasis. To reveal the molecular role of OPTN in muscle atrophy, we used cultured C2C12 myotubes treated with tumor necrosis factor-like inducer of apoptosis (TWEAK) as an in vitro model of muscle atrophy. Our data showed that OPTN had no effect on the process of muscle atrophy in this model. On the other hand, we found that myogenic differentiation was affected by OPTN. Immunoblotting analysis showed that OPTN protein levels gradually decreased during C2C12 differentiation. Furthermore, OPTN knockdown inhibited C2C12 differentiation, accompanied by reduction of mRNA and protein expression levels of myogenin and MyoD. These findings suggested that OPTN may have a novel function in muscle homeostasis and play a role in the pathogenesis of neuromuscular diseases.

Synchronization of neural activity, especially at the gamma band, contributes to perceptual functions. In several psychiatric disorders, deficits of perceptual functions are reflected in synchronization abnormalities. Plausible cause of this impairment is an alteration in the balance between excitation and inhibition (E/I balance); a disruption in the E/I balance leads to abnormal neural interactions reminiscent of pathological states. Moreover, the local lateral excitatory-excitatory synaptic connections in the cortex exhibit excitatory postsynaptic potentials (EPSPs) that follow a log-normal amplitude distribution. This long-tailed distribution is considered an important factor for the emergence of spatiotemporal neural activity. In this context, we hypothesized that manipulating the EPSP distribution under abnormal E/I balance conditions would provide insights into psychiatric disorders characterized by deficits in perceptual functions, potentially revealing the mechanisms underlying pathological neural behaviors. In this study, we evaluated the synchronization of neural activity with external periodic stimuli in spiking neural networks in cases of both E/I balance and imbalance with or without a long-tailed EPSP amplitude distribution. The results showed that external stimuli of a high frequency lead to a decrease in the degree of synchronization with an increasing ratio of excitatory to inhibitory neurons in the presence, but not in the absence, of high-amplitude EPSPs. This monotonic reduction can be interpreted as an autonomous, strong-EPSP-dependent spiking activity selectively interfering with the responses to external stimuli. This observation is consistent with pathological findings. Thus, our modeling approach has potential to improve the understanding of the steady-state response in both healthy and pathological states.

We propose FrictionalMonolith , a monolithic pressure-friction-contact solver for more accurately, robustly, and efficiently simulating two-way interactions of rigid bodies with continuum granular materials or inviscid liquids. By carefully formulating the components of such systems within a single unified minimization problem, our solver can simultaneously handle unilateral incompressibility and implicit integration of friction for the interior of the continuum, frictional contact resolution among the rigid bodies, and mutual force exchanges between the continuum and rigid bodies. Our monolithic approach eliminates various problematic artifacts in existing weakly coupled approaches, including loss of volume in the continuum material, artificial drift and slip of the continuum at solid boundaries, interpenetrations of rigid bodies, and simulation instabilities. To efficiently handle this challenging monolithic minimization problem, we present a customized solver for the resulting quadratically constrained quadratic program that combines elements of staggered projections, augmented Lagrangian methods, inexact projected Newton, and active-set methods. We demonstrate the critical importance of a unified treatment and the effectiveness of our proposed solver in a range of practical scenarios.

ADSSL1 myopathy is an inherited myopathy with limb weakness, respiratory muscle paralysis, dysphagia, and myocardial symptoms. We present an autopsy case of a 66-year-old male carrying compound heterozygous variants c.781G>A (p.D261N) and c.919delA (p.I307fs) in ADSSL1. He had not run fast since school with no family history. He showed a gradual progression of limb weakness and developed dyspnoea, dysphagia, and Brugada syndrome at the age of 56. The magnetic resonance imaging (MRI) revealed bright tongue sign. Muscle biopsy showed only chronic myopathic changes. He died of respiratory muscle weakness at the age of 66. Autopsy revealed that there were many fibres with vacuoles and nemaline rods in the biceps brachii, tongue, diaphragm, and iliopsoas. Many lipopigments and nuclear clumps were also detected. The myocardium and central nervous system had only nonspecific age-related changes. This is the first autopsied case to clarify the terminal state of ADSSL1 myopathy.

Background: This study investigated the clinical factors related to hospital-acquired disability (HAD) among 70 patients (median age, 78 years; interquartile range (IQR), 78 - 83) who were hospitalized for heart failure (HF) at Ayase Heart Hospital between December 2019 and October 2020. Methods: HAD was defined as a >= 5-point decrease in Barthel Index (BI) scores from admission to discharge. Twenty-nine HF patients (41%) developed HAD after admission. Results: Compared to the non-HAD group, the HAD group had higher Kihon Checklist scores (14 points (IQR, 11 - 17) vs. 9 points (IQR, 6 - 13); P < 0.01) and prevalence of multi-faceted frailty (90% vs. 29%; P < 0.01), a longer urinary-catheter-placement period (3 days (IQR, 1 - 5] vs. 1 day (IQR, 0 - 2), P < 0.05), less daily number of steps (457 steps (IQR, 301 - 997) vs. 1,692 steps (IQR, 1,227 - 2,418); P < 0.01), and moderate-intensity physical activity time (0 min (IQR, 0 - 2] vs. 1 min (IQR, 0 - 3); P < 0.05). Conclusion: In conclusion, lower physical function and general physical activity and longer urinary-catheter-placement are associated with HAD. Cardiol Res. 2021;12(5):293-301 doi: https://doi.org/10.14740/cr1306

Although sepsis is known to cause functional decline, the prevalence and predictors of hospital-acquired functional decline (HAFD) in patients with sepsis are unclear. The purpose of this study was to investigate the prevalence and predictors of HAFD in patients with sepsis admitted to the ICU. This study is a single-center retrospective observational study from January 2014 to December 2019. We included all consecutive patients with sepsis who received rehabilitation in our ICU. The primary outcome was HAFD, which was defined as a decrease in at least five points of the Barthel index mobility score from prehospital to hospital discharge. We described the prevalence of HAFD and investigated the predictors of HAFD using the multivariate logistic regression analysis adjusting for potential confounders. Among 134 patients, 57 patients (42.5%) had HAFD. The longer time to initial ambulation and lower prehospital walking ability were associated with HAFD (adjusted odds ratio [OR] 1.07; 95% confidence interval [CI], 1.03-1.10 and adjusted OR 0.79; 95% CI, 0.66-0.95, respectively). In conclusion, nearly half of the patients with sepsis who received rehabilitation developed HAFD. Lower functional status prior to hospitalization and the longer time to initial ambulation was associated with HAFD, indicating the potential importance of early ambulation among septic patients in the ICU.

Renal dysfunction is an independent predictor of adverse outcomes in patients with coronary artery disease (CAD). However, the prognostic impact of mid-term changes in renal dysfunction status remains unclear. This study aimed to investigate the impact of mid-term changes in renal dysfunction status on long-term clinical outcomes in CAD patients who underwent percutaneous coronary intervention (PCI).We enrolled 382 consecutive patients with CAD who underwent PCI. Renal dysfunction was defined as a reduced estimated glomerular filtration rate (eGFR) of ＜60 mL/min/1.73mAt baseline, renal dysfunction was observed in 77 patients (20%). At the 1-year follow-up, new-onset renal dysfunction was observed in 46 patients (12%), and 59 patients (15%) had persistent renal dysfunction. Kaplan-Meier analysis revealed a significantly higher event rate in patients with persistent renal dysfunction and new-onset renal dysfunction (log-rank test, P=0.0003). In the multivariate Cox proportional hazards analysis, persistent renal dysfunction and new-onset renal dysfunction were independently associated with composite events after adjusting for confounding factors (adjusted hazard ratios 4.08 and 2.64, 95% confidence intervals 1.72-9.57 and 1.03-6.31, P=0.0016, P=0.0045, respectively).Persistent and new-onset renal dysfunction at 1-year follow-up were associated with unfavorable outcomes in patients with CAD who underwent PCI.

In recent years, as a treatment for mental disorders in addition to drug treatment, a non-drug treatment called chronotherapy has been attracting attention. However, the achievement of optimized chronotherapy for each subject's condition requires that the disturbance of the patient's circadian rhythm must be captured over a long duration. Therefore, it is necessary to develop biomarkers that are easy to measure, quantitative, and continuously measured. Complexity analysis of electroencephalograms revealed specific patterns related to circadian rhythms. However, such complexity analysis cannot capture variability in spatial patterns, although moment-to-moment temporal dynamic characteristics can be captured. Therefore, it is necessary to evaluate the dynamic characteristics of the interaction of neural activity throughout the brain. To evaluate the dynamic whole-brain interaction, we proposed a new microstate approach based on the instantaneous frequency distribution. In this context, we hypothesized that it would be possible to detect circadian rhythms using the microstate approach. In this study, to clarify the dynamic interactions of the entire neural network of the brain by circadian rhythms, we measured EEG data at day and night, and detected dynamic state transitions based on the instantaneous frequency distribution of the whole brain from EEG. The results showed the probability of transition among region-specific phase-leading states related to circadian rhythms. This finding might be widely utilized to detect circadian rhythms in healthy and pathological conditions.

Background Peak oxygen uptake (peak VO2) is known not only as an index of aerobic fitness but also one of an index of life expectancy. Frailty, sarcopenia, and cachexia are associated with a poor prognosis and high mortality. The purpose of this study was to determine the relationships of peak VO2 with the features of sarcopenia, frailty, and cachexia, to provide insight into which might mediate the poor prognosis. Methods The first group of participants was 175 community‐dwelling older Japanese outpatients (58 men and 117 women; mean age 77.6 ± 6.4 years), in whom we assessed the features of sarcopenia, frailty, and cachexia, and measured peak VO2 during cardiopulmonary exercise. To confirm the relationships, we analysed another group of 162 participants (77.3 ± 5.5 years). Results There were significant correlations between peak VO2 and the features of sarcopenia, frailty, and cachexia, with the exception of high sensitivity C‐reactive protein. Multiple linear regression analysis for the prediction of peak VO2 (mL/min) identified following formula: predicted peak VO2 = −11.6 × age (years) + 25.5 × haemoglobin concentration (g/dL) + 114.2 × skeletal muscle mass index (kg/m2) + 8.9 × hand grip strength (kg) + 226.4 × usual walking speed (m/s) − 65.8 × fatiguability (absence 0, presence 1) − 177.4 × chronic heart failure (absence 0, presence 1) + 437.1 (R2 = 0.627, P

We introduce an efficient differentiable fluid simulator that can be integrated with deep neural networks as a part of layers for learning dynamics and solving control problems. It offers the capability to handle one-way coupling of fluids with rigid objects using a variational principle that naturally enforces necessary boundary conditions at the fluid-solid interface with sub-grid details. This simulator utilizes the adjoint method to efficiently compute the gradient for multiple time steps of fluid simulation with user defined objective functions. We demonstrate the effectiveness of our method for solving inverse and control problems on fluids with one-way coupled solids. Our method outperforms the previous gradient computations, state-of-the-art derivative-free optimization, and model-free reinforcement learning techniques by at least one order of magnitude.

Objective Early mobilization and rehabilitation has become common and expectations for physical therapists working in intensive care units have increased in Japan. The objective of this study was to establish consensus-based minimum clinical practice standards for physical therapists working in intensive care units in Japan. It also aimed to make an international comparison of minimum clinical practice standards in this area. Methods In total, 54 experienced physical therapists gave informed consent and participated in this study. A modified Delphi method with questionnaires was used over three rounds. Participants rated 272 items as "essential/unknown/non-essential". Consensus was considered to be reached on items that over 70% of physical therapists rated as "essential" to clinical practice in the intensive care unit. Results Of the 272 items in the first round, 188 were deemed essential. In round 2, 11 of the 62 items that failed to reach consensus in round 1 were additionally deemed essential. No item was added to the "essential" consensus in round 3. In total, 199 items were therefore deemed essential as a minimum standard of clinical practice. Participants agreed that 42 items were not essential and failed to reach agreement on 31 others. Identified 199 items were different from those in the UK and Australia due to national laws, cultural and historical backgrounds. Conclusions This is the first study to develop a consensus-based minimum clinical practice standard for physical therapists working in intensive care units in Japan.

Aims Functional decline is associated with worse outcomes in patients with elderly heart failure (HF), but little is known about the prognostic impact of hospital‐acquired disability (HAD) during hospital stay after acute HF. The present study examines the prognostic significance of HAD in the prediction of all‐cause mortality in elderly patients who admitted for acute HF. Methods and results This retrospective study was performed in 1941 elderly patients aged ≥65 years or older from the cardiovascular physiotherapy for acute HF patients in the Tokyo metropolitan area registry and excluded those who died in hospital. HAD was defined as any decline in the Barthel index (BI) before discharge compared with the BI within 1 month before hospital admission. The primary outcome of this study was all‐cause death and HF readmission. A total of 565 (29%) deaths and 789 (41%) HF readmission occurred over a median follow‐up period of 1.7 years. A total of 476 patients (25%) had HAD during hospital stay after acute HF. In multivariable analysis, HAD predicted all‐cause death [hazard ratio (HR): 1.772; 95% confidence interval (CI): 1.450–2.167; P

Female sex in patients with atrial fibrillation (AF) is a controversial and paradoxical risk factor for stroke—controversial because it increases the risk of stroke only among older women of some ethnicities and paradoxical because it appears to contradict male predominance in cardiovascular diseases. However, the underlying mechanism remains unclear. We conducted simulations to examine the hypothesis that this sex difference is generated non-causally through left truncation due to competing risks (CR) such as coronary artery diseases, which occur more frequently among men than among women and share common unobserved causes with stroke. We modeled the hazards of stroke and CR with correlated heterogeneous risk. We assumed that some people died of CR before AF diagnosis and calculated the hazard ratio of female sex in the left-truncated AF population. In this situation, female sex became a risk factor for stroke in the absence of causal roles. The hazard ratio was attenuated in young populations without left truncation and in populations with low CR and high stroke incidence, which is consistent with real-world observations. This study demonstrated that spurious risk factors can be identified through left truncation due to correlated CR. Female sex in patients with AF may be a paradoxical risk factor for stroke.

Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO2) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO2 (β = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

The aim of the present study was to clarify the effect of electrical muscle stimulation (EMS) on the spatial distribution pattern of electromyographic activity in healthy young adults using multi-c...

In recent years, expectations have increased for the development of filters for removing air pollutants. Rayon fibers have rough surfaces and excellent adsorption characteristics. Therefore, rayon is a promising material for such filters. By further roughening its surface, its adsorptivity to substances such as volatile organic compounds can likely be improved. The surface of rayon fibers was roughened via wet spinning carried out by adding oleic acid to a raw viscose. As a result, porous fibers containing several pores with a diameter of about 0.5–1.0 µm were obtained. A weight reduction treatment of the porous rayon fibers with cellulase, a cellulose-degrading enzyme, resulted in the appearance of several streaks and asperities on their surfaces. To investigate the adsorption behavior of the rayon fibers after cellulase treatment, dye adsorption was examined using an aqueous methylene blue solution. The porous rayon fibers adsorbed much more dye than the regular fibers. In addition, the fibers absorbed more dye after treatment with cellulase than without treatment in both fibers. The deodorizing function of the rayon fibers was also investigated using ammonia gas. The porous rayon fibers treated with cellulase had a very high deodorizing effect. In the proposed study, rayon fibers (which are porous inside) were treated with cellulase, and their surface was found to be considerably rough.

Aim Although it is known that geriatric syndrome is associated with the development of frailty, it is not known whether an amelioration of geriatric syndrome also improves shared risk factors and frailty. Methods In total, 67 community‐dwelling older people (79.6 ± 6.5 years, 49 women) participated in this study (41 were classified as pre‐frail and 26 as frail). We analyzed indices of physical frailty and cognitive depression, exercise tolerance and health‐related quality of life as frailty related indices, and the participants completed a questionnaire regarding common geriatric symptoms (cold extremities, leg edema, breathlessness, urinary incontinence, chronic headache, chronic pain, a sense of numbness, anorexia, constipation, insomnia and skin trouble) using numeric ratings. Frailty was evaluated using the Japanese version of the Cardiovascular Health Study (J‐CHS) criteria. The participants then underwent a far‐infrared low‐temperature sauna (FILTS) program twice a week for 3 months and the above parameters were reassessed. Results After the FILTS program, there were significant differences in usual walking speed, peak oxygen uptake, Geriatric Depression Scale‐15, health‐related quality of life and the severity of several geriatric symptoms. Of the 67 participants, 18 showed improvements in their J‐CHS frailty score, 47 showed no change and two showed reductions. Linear regression analysis showed that the change in the numeric rating of the coldness of extremities (B = −0.105, P = 0.013) and the cumulative numeric rating for geriatric syndromes (B = 0.044, P

Laparoscopic sleeve gastrectomy (LSG) is an important therapeutic option for morbidly obese patients. Although LSG promotes sufficient weight loss, how LSG changes plasma metabolites remains unclear. We assessed changes in plasma metabolite levels after LSG. We collected plasma samples from 15 morbidly obese Japanese patients before and 3 months after LSG. A total of 48 metabolites were quantified using capillary electrophoresis time‐of‐flight mass spectrometry‐based metabolomic profiling. Branched chain amino acids, several essential amino acids, choline, 2‐hydroxybutyric acid, 2‐oxoisovaleric acid and hypoxanthine were significantly decreased after LSG. Tricarboxylic acid cycle metabolites, including citric acid, succinic acid and malic acid, were significantly elevated after LSG. This is the first report to show dynamic alterations in plasma metabolite concentrations, as assessed using capillary electrophoresis time‐of‐flight mass spectrometry, in morbidly obese patients after LSG. Our results might show how LSG helps improve obesity, in part through metabolic status changes, and propose novel therapeutic targets to ameliorate obesity., Dynamic alterations in plasma metabolite concentrations in morbidly obese patients after laparoscopic sleeve gastrectomy.

In recent years, the importance of early physiotherapy for rapid mental and physical functional recovery is increasing with the increasing number of older patients and high-risk patients with duplicate disorders. Increasing the effectiveness of acute physiotherapy within a shorter hospital stay is a great challenge. We published the first expert consensus of early rehabilitation in Asia in 2017. Our expert consensus will contribute to the establishment of physiotherapy in intensive care for Asian populations. The minimum standard of clinical practice for physiotherapists working in critical care settings is important to showcase physiotherapists’ knowledge and abilities as medical professionals working in the intensive care unit. We are planning to release the minimum standard of clinical practice for Japanese physiotherapists working in critical care settings in 2020. Being in the forefront among nations of aging populations, Japan has a rapidly increasing number of older frail patients with heart failure. Further studies are necessary to confirm the effectiveness of task-specific exercise training considering the characteristics of frailty.

Although there are several case reports of progressive multifocal leukoencephalopathy (PML) in multiple myeloma (MM), there are few reports of cases associated with pomalidomide. Here, we report the case of a 69-year-old female who had received 41 cycles of pomalidomide and dexamethasone treatment for relapsed/refractory IgG-κ MM presented with right-hand weakness; she was diagnosed as pomalidomide-associated PML. Fluid-attenuated inversion recovery (FLAIR) on admission showed high signals in the bilateral front-parietal lobe white matter, with multiple punctate lesions in the vicinity of the main lesions. These punctate pattern findings on FLAIR were similar to that of natalizumab-associated PML. Susceptibility weighted imaging (SWI) showed hypointense rims within the cortex at unaffected sites, in the initial stages. Subsequently, the clinical manifestations deteriorated, and the FLAIR images showed new hyperintense white matter lesions at the sites where cortical SWI hypointense rims were detected on the initial MRI examination. Our patient's serial MRI findings suggest that cortical SWI hypointense rims appear prior to the visible demyelinating white matter lesions in patients with PML.

Objective: Activation of nicotinic acetylcholine receptors (nAChRs) results in neuroprotection via a poorly understood molecular mechanism. In this study, we aimed to investigate the effect of nACh...

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p

Background: The frailty state consists of not only physical but also psycho-emotional problems, such as cognitive dysfunction and depression as well as social problems. However, few reports have examined the relationship between frailty and anxiety levels in elderly patients undergoing cardiac rehabilitation (CR). Methods: We analyzed 255 patients (mean age: 74.9 ± 5.8 years, 67% male) who participated in early phase II CR at Juntendo University Hospital. At the beginning of CR, patients carried out self-assessments based on the Kihon Checklist (KCL) and the State Trait Anxiety Inventory Form (STAI). Patients were divided into three groups: frailty group (n = 99, 39%), pre-frailty group (n = 81, 32%), and non-frailty group (n = 75, 29%) according to the KCL. We assessed results from the KCL scores and its relationship with anxiety levels. Results: Among the three groups, there were no significant differences in age, underlying illnesses, or the prevalence of coronary risk factors. Depressive mood domains of the KCL were significantly higher in the frailty and pre-frailty groups than in the non-frailty groups (3.0 ± 1.5 vs. 1.4 ± 1.2 vs. 0.4 ± 0.6; P < 0.01). The state anxiety level was significantly higher in the frailty group than in the non-frailty group (41.6 ± 0.9 vs. 34.9 ± 1.0; P < 0.01). The trait anxiety levels were significantly higher in the frailty group and pre-frailty group than in the non-frailty group (45.5 ± 0.9 vs. 39.2 ± 1.0 vs. 35.1 ± 1.1; P < 0.01). State anxiety and trait anxiety also showed a significantly positive correlations with the KCL scores (r = 0.32 vs. 0.41, P < 0.01). Conclusions: Frailty scores were positively correlated not only with physical function but also with depression mood and anxiety levels in elderly patients undergoing early phase II CR. These results suggest that assessment of depressive mood and anxiety is also important in elderly patients undergoing early phase II CR. Cardiol Res. 2020;11(6):405-411 doi: https://doi.org/10.14740/cr1165

Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells.

Heart failure and frailty share aging as a strong risk factor. The prevalence of frailty has been shown to be particularly high in elderly patients with heart failure. Moreover, it is important not to confine frailty to physical aspects. Rather, it should be considered to consist of multiple domains, including physical disability, psychiatric disorders, cognitive impairment, depression, and social disconnection. Development of interventions that can improve frailty domains are not well established, although observational studies have evaluated the association of various frailty domains and their prognostic impact. Some interventions, including resistance exercise, functional exercise, and respiratory muscle training have been demonstrated to hold potential for improving physical frailty. In terms of cognitive dysfunction, previous studies have demonstrated that exercise therapy is also effective for cognitive dysfunction. The social domain of frailty is one of the least investigated domains, particularly in patients with heart failure. However, heart failure is also strongly associated with physical frailty and cognitive impairment and has a poor prognosis in old patients. The prevalence of social frailty in elderly patients who need hospitalization due to heart failure is higher than previously thought. Very few studies have tested interventions targeting social frailty. Frailty and heart failure affect each other, and both are becoming increasingly important in society. In this article, we review the physical, cognitive, and social domains of frailty and the possible interventions to improve them in patients with heart failure.

A recent study demonstrated that continuous positive airway pressure (CPAP) may exacerbate obstructive sleep apnea (OSA) in patients with multiple system atrophy (MSA) and a floppy epiglottis (FE) as the CPAP promotes downward displacement of the epiglottis into the laryngeal inlet. In this case series, we examined the effectiveness of an oral appliance (OA) for treating OSA in three patients with MSA and an FE.Patients with MSA were demonstrated to have an FE on fiberoptic laryngoscopy under sedation using intravenous propofol. The therapeutic intervention was fitting an OA. Polysomnography (PSG) was performed subsequently with the OA in place.In three patients with MSA, some parameters used to assess the severity of OSA improved with an OA. Both apnea-hypopnea index (AHI) and arousal index (ArI) decreased while wearing the OA in two cases while in the third case, apnea index (AI) and cumulative time at peripheral oxygen saturation (SpOOA therapy using a two-piece type mandibular advancement device (MAD) may be a useful treatment intervention for patients with OSA who have MSA and FE.

Locus coeruleus (LC) overactivity, especially in the right hemisphere, is a recognized pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and may be related to inattention. LC activity synchronizes with the kinetics of the pupil diameter and reflects neural activity related to cognitive functions such as attention and arousal. Recent studies highlight the importance of the complexity of the temporal patterns of pupil diameter. Moreover, asymmetrical pupil diameter, which correlates with the severity of inattention, impulsivity, and hyperactivity in ADHD, might be attributed to a left-right imbalance in LC activity. We recently constructed a computational model of pupil diameter based on the newly discovered contralateral projection from the LC to the Edinger–Westphal nucleus (EWN), which demonstrated mechanisms for the complex temporal patterns of pupil kinetics; however, it remains unclear how LC overactivity and its asymmetry affect pupil diameter. We hypothesized that a neural model of pupil diameter control featuring left-right differences in LC activity and projections onto two opponent sides may clarify the role of pupil behavior in ADHD studies. Therefore, we developed a pupil diameter control model reflecting LC overactivity in the right hemisphere by incorporating a contralateral projection from the LC to EWN and evaluated the complexity of the temporal patterns of pupil diameter generated by the model. Upon comparisons with experimentally measured pupil diameters in adult patients with ADHD, the parameter region of interest of the neural model was estimated, which was a region in the two-dimensional plot of complexity versus left-side LC baseline activity and that of the right. A region resulting in relatively high right-side complexity, which corresponded to the pathophysiological indexes, was identified. We anticipate that the discovery of lateralization of complexity in pupil diameter fluctuations will facilitate the development of biomarkers for accurate diagnosis of ADHD.

Cardiac rehabilitation (CR) in the long term is fundamental to achieve better outcomes. However, most patients may find it difficult to maintain healthy lifestyle behavior after ambulatory CR program. We aimed to investigate the feasibility on remote CR support program (Remote-CR) in older patients with cardiac disease.Between October 2020 and February 2021, we enrolled older patients with cardiac disease after at least over 5 months of ambulatory CR program. The study was conducted as a randomized controlled case series to compare Remote-CR vs. center-based CR (CB-CR) after ambulatory CR in older patients with cardiac disease. The core component of Remote-CR is a web application, which evaluates vital sign and receives feedback through real-time video consultation once a week. We evaluated the satisfaction of Remote-CR, and impact of Remote-CR on adherence to exercise and physical activity management. Moreover, we assessed the change in functional status using handgrip strength, usual gait speed, short physical performance battery (SPPB), and Kihon checklist (KCL) before the intervention, at the end of the 4-week intervention, and cardiovascular-related hospital discharge within 6 months after completion of ambulatory CR.Eleven patients were enrolled (six for Remote-CR and five for CB-CR). All participants completed the intervention without serious adverse event in each group. After the on-site initial remote system set up, all the patients completed the Remote-CR session without on-site assistance. Patients' satisfaction with Remote-CR was generally high. Remote-CR helps to maintain healthy lifestyle behavior. In addition, Remote-CR and CB-CR seem to be equally successful in maintaining functional status and preventing cardiovascular-related hospital readmission.This trial suggested the Remote-CR comprising a hybrid of information and communication technology and strategy for health behavior change may be a feasible and safe intervention option in selected older patients with cardiac disease after completion of ambulatory CR.

Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer's disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells.

Background Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. This study aimed to investigate the associations between SAF and MACE risk in patients with HF who underwent CR. Methods This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. Major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2017. Results Patients’ mean age was 68.1 years, and 61% were male. Patients were divided into two groups according to the median SAF levels (High and Low SAF groups). Patients in the High SAF group were significantly older, had a higher prevalence of chronic kidney disease, and more frequently had history of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a mean follow-up period of 590 days, 18 patients had all-cause mortality and 36 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P Conclusion SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who underwent CR.