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Objectives: Currently available questionnaires have limited ability to measure physical activity (PA) using accelerometers as a gold standard. This study aimed to develop a PA questionnaire for middle-aged Japanese workers and propose a PA scoring system for predicting low moderate-to-vigorous PA (MVPA)., Methods: A total of 428 participants (median age 49 years; 75.8% men) participated in a 7-day PA measurement using an accelerometer and a questionnaire. The association between questionnaire responses and low MVPA (<150 min/wk) was assessed by logistic regression analysis. A score was assigned to each response based on the correlation coefficients of the multivariate model. The ability of the sum score to predict low MVPA was assessed using the area under the receiver operating characteristic curve (AUC)., Results: Five questionnaire items were used for measuring PA scores (range: 0-50; higher scores indicated a higher probability of low MVPA). The AUC was 0.741 (95% CI, 0.689-0.792), and the sensitivity and specificity at the optimal cut-off value were 66.7% and 68.2%, respectively. This predictive ability was slightly increased by body mass index (AUC 0.745 [95% CI, 0.693-0.796]; sensitivity 69.9%; specificity 66.9%). These predictive values were greater than those of conventional questionnaires used in health checkups in Japan (P < .05)., Conclusions: This questionnaire-based PA scoring system showed moderate accuracy in predicting low MVPA. It is useful for screening physically inactive workers and promoting PA., (© The Author(s) [2023]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

Background: Elderly patients with acute myocardial infarction (AMI) are a high-risk population for heart failure (HF), but the association between physical frailty and worsening prognosis, including HF development, has not been documented extensively., Methods and results: As part of the FLAGSHIP study, we enrolled 524 patients aged ≥70 years hospitalized for AMI and capable of walking at discharge. Physical frailty was assessed using the FLAGSHIP frailty score. The primary outcome was a composite outcome of all-cause death and HF rehospitalization within 2 years after discharge. The secondary outcome was all-cause death and HF rehospitalization. After adjusting for confounders, physical frailty showed a significant association with an increased risk of the composite outcome (hazard ratio [HR]=2.09, 95% confidence interval [CI]: 1.03-4.22, P=0.040). The risk of HF rehospitalization increased with physical frailty, but the association was not statistically significant (HR=2.14, 95% CI: 0.84-5.44, P=0.110). Physical frailty was not associated with an increased risk of all-cause death (HR=1.45, 95% CI: 0.49-4.26, P=0.501)., Conclusions: The findings suggest that physical frailty assessment serves as a stratifying tool to identify high-risk populations for post-discharge clinical events among ambulant elderly patients with AMI.

The redox state of human serum albumin (HSA) is reported to be an oxidative stress biomarker; however, its clinical use in cardiac disease has not yet been examined. This study aimed to investigate the relation between the redox state of HSA and exercise capacity, which is a robust prognostic factor, in patients with cardiovascular disease. This cross-sectional study included outpatients with cardiac disease. Exercise capacity was assessed by peak oxygen consumption (peakVO 2 ) measured using symptom-limited cardiopulmonary exercise testing. The high-performance liquid chromatography postcolumn bromocresol green method was used to part HSA into human nonmercaptalbumin (oxidized form) and human mercaptalbumin (HMA, reduced form). The fraction of human mercaptalbumin found in HSA (f[HMA]) was calculated as an indicator of the redox state of HSA. The association between peakVO 2 and f(HMA) was examined using the Spearman correlation coefficient and multivariate linear regression analysis. A total of 70 patients were included (median age 76 years; 44 men; median peakVO 2 15.5 ml/kg/min). The f(HMA) was positively correlated with peakVO 2 (r = 0.38, p <0.01). Even after controlling for potential confounders, this association remained in the multivariate linear regression analysis (standardized beta = 0.24, p <0.05). We found a positive association between f(HMA) and peakVO 2 , independent of potential confounders in patients with cardiac disease, suggesting that f(HMA) may be a novel biomarker related to exercise capacity in cardiac disease. Longitudinal studies are required to further examine the prognostic capability of f(HMA), the responsiveness to clinical intervention, and the association between f(HMA) and cardiac disease., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Insights from recent clinical trial testing revascularization strategies have interested interventional cardiologists in optimal medical therapy and secondary prevention modalities. As no large-scale survey has been recently conducted, this report presents the results of a nationwide survey on interventionists' concerns regarding secondary prevention after percutaneous coronary intervention (PCI) and discusses medical support system needs in Japan. A questionnaire to assess the status and challenges of secondary prevention interventions by interventional cardiologists during outpatient visits was supplied to Cardiovascular Interventional Technology (CVIT)-certificated hospitals. This was answered by representative cardiologists of each hospital and comprised three queries: (1) the necessity of outpatient cardiac rehabilitation to promote post-PCI lifestyle guidance; (2) the feasibility of providing lifestyle guidance; and (3) the barriers to lifestyle guidance, during outpatient visits. Questions 1 and 2 were answered using a 5-point Likert scale. Survey responses were received from 391 hospitals (54.9% of 712 CVIT-certificated facilities). For Question 1, 327 hospitals (84.1%) answered "agree", and 386 hospitals (98.7%) answered "agree" or "somewhat agree". For Question 2, 10% of hospitals answered "agree", and "agree" and "somewhat agree" amounted to less than 50%. For Question 3, 83.5% of the facilities answered lack of time as the major reason). The next reasons included an early reverse referral to family doctors after PCI, and a lack of managerial advantage (60% and 40% of the hospitals, respectively). In conclusion, interventionists are concerned about secondary prevention for their patients. The issues clarified in the survey will be important for developing next-generation secondary prevention systems., (© 2022. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: The Short Physical Performance Battery (SPPB) has been reported to predict clinical outcomes in patients with heart failure (HF). However, whether the discriminative capacity of SPPB score for adverse outcomes varies according to the phenotypes of HF, such as HF with reduced, mid-range, and preserved left-ventricular ejection fraction (HFrEF, HFmrEF, and HFpEF) remains unclear. The aim of this study was to investigate the difference in discriminative capacity of SPPB score for predicting 2-year mortality among phenotypes of HF., Methods: We consecutively enrolled 542 adult patients admitted for HF (HFrEF, n = 187; HFmrEF, n = 94; HFpEF, n = 261). The patients underwent SPPB score when discharged from hospital. The primary endpoint was all-cause mortality during the 2 years after hospital discharge. We assessed the discriminative capacity of SPPB score for predicting mortality by using receiver operating characteristic (ROC) curve analysis., Results: A total of 95 events (17.5%) occurred during the follow-up period. The area under the curve of ROC (95% confidence interval) was 0.80 (0.71-0.88) in HFrEF, 0.61 (0.46-0.76) in HFmrEF, and 0.70 (0.61-0.79) in HFpEF group. After adjustment for potential confounders, the hazard ratios (95% confidence interval) of the lower SPPB score were 5.38 (2.34-14.6) in HFrEF group, 1.12 (0.36-3.29) in HFmrEF group, and 3.19 (1.68-6.22) in HFpEF group., Conclusions: Prognostic value of SPPB score varies according to the HF phenotype. SPPB score predicts mortality in patients with HFrEF and HFpEF, but not in patients with HFmrEF. These findings lead to more precise risk prediction by SPPB score in patients with HF., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Niemann-Pick disease type C (NPC) is caused by a loss of function of either NPC1 or NPC2 protein, resulting in the accumulation of unesterified, free-cholesterol (free-C) in cells/tissues and thus leading to cell/tissue damage. In the brain of patients/animals with NPC, as a consequence of the accumulation of free-C in late endosomes/lysosomes (LE/LY) in cells, multiple lipids including complex sphingolipids are accumulated, and almost all patients/animals ultimately develop progressive/fatal neurodegeneration. Several reagents that are considered to act in the brain show beneficial effects on NPC-model animals. In the present study, we investigated the effects of antiepileptic drugs, such as primidone and valproic acid, on the accumulation of free-C in NPC1-null CHO cells and NPC1* fibroblasts, human fibroblasts established from a patient with NPC1 mutation. Like valproic acid, treatment with primidone reduced free-C levels in LE/LY in NPC1-null/mutant cells. Down-regulation of cholesterol ester levels in NPC1-null cells and up-regulation of HMG-CoA reductase and low-density lipoprotein receptor mRNA levels in NPC1* cells were partially recovered by primidone treatment. Thus, primidone was suggested to enhance free-C trafficking from LE/LY to endoplasmic reticulum in NPC1-null/mutant cells. In NPC1-null mice, oral application of primidone (100 mg/kg/day) extended lifespan by approximately 5 days, although the first days showing ataxia, a typical symptom of neuromotor dysfunction, were not affected. Our findings suggest the potential of primidone for the treatment of NPC., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: Oxidative stress plays a key role in declining exercise capacity, which is one of the major health problems in old age. The redox state of human serum albumin (HSA) has been considered a biomarker reflecting oxidative stress; however, its relationship to exercise capacity in older people remains to be examined. We aimed to examine the redox state of HSA as a potential biomarker of exercise capacity in community-dwelling older women., Methods: We analyzed 125 women aged ≥75 years. Exercise capacity was evaluated using 6-min walk distance (6MWD). The redox state of HSA was analyzed using the high-performance liquid chromatography post-column bromocresol green reaction method. The fraction of human mercaptalbumin in HSA (f[HMA]) was considered the redox state of HSA. Pearson's correlation coefficient (r) or Spearman's correlation coefficient (ρ) was used to assess correlations between 6MWD, f(HMA) and HSA. The association between 6MWD and f(HMA) was further examined using multivariate linear regression analysis adjusted for age, diabetes mellitus, renal function, number of medications, HSA and knee extensor isometric strength., Results: The 6MWD was significantly correlated with f(HMA; ρ = 0.44, P < 0.001), but not with HSA (r = 0.05, P = 0.562). The f(HMA) was not significantly correlated with HSA (ρ = 0.03, P = 0.769). Multivariate linear regression analysis showed that f(HMA) was independently associated with 6MWD (standardized β = 0.27, P = 0.004)., Conclusions: The findings of this study suggest that f(HMA) might serve as a novel biomarker for exercise capacity in community-dwelling older women. Geriatr Gerontol Int 2019; ••: ••-••., (© 2019 Japan Geriatrics Society.)

Background: The combined effects of physical inactivity and obesity on hypertension have been recognized; however, previous studies evaluated physical activity using questionnaires. We aimed to examine the effects of physical activity, measured using an accelerometer, and obesity on hypertension onset., Methods: At baseline, 426 middle-aged Japanese men who were not on antihypertensive medications were included. Physical activity was measured for 7 consecutive days using an accelerometer. Mean daily moderate to vigorous physical activity (MVPA) and step count (SC) were calculated. Low MVPA and low SC were each defined as the first tertile. Obesity was defined as ≥25 kg/m2 of body mass index. The onset of hypertension was defined as receiving antihypertensive agents during the 4-year follow-up. The combined effects of obesity and physical inactivity on hypertension were examined using Cox regression analysis. Potential confounders included age, smoking, alcohol consumption, daily salt intake, dyslipidemia, diabetes mellitus, and systolic and diastolic blood pressures., Results: Cox regression analysis revealed that both obesity and low MVPA predicted hypertension in patients, independent of confounders (hazard ratio [HR]: 2.64, 95% confidence interval [CI]: 1.08-6.42, p = 0.033), unlike obesity alone (HR: 1.50, 95% CI: 0.50-3.26, p = 0.590). Stratification by obesity and SC revealed similar hypertension risks among the two groups (Obesity with low SC [HR: 2.10, 95% CI 0.88-5.24, p = 0.089]; Obesity without low SC [HR: 1.72, 95% CI 0.93-4.01, p = 0.082])., Conclusions: Here, findings suggest that the coexistence of obesity and decreased MVPA may increase the risk of hypertension onset., (Copyright © 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Ceramide kinase (CerK) phosphorylates ceramide to ceramide-1-phosphate (C1P), and various roles for the CerK/C1P pathway in the regulation of cellular/biological functions have been demonstrated. CerK is constitutively phosphorylated at several serine (Ser, S) residues, however, the roles of Ser residues, including their phosphorylation, in CerK activity, have not yet been elucidated in detail. Therefore, we conducted the present study to investigate this issue. In A549 cells expressing wild-type CerK, a treatment with phorbol 12-myristate 13-acetate (PMA) decreased the formation of C1P in a protein kinase C (PKC)-βI/II-mediated manner. In the Phos-tag SDS-PAGE analysis, CerK existed in its phosphorylated form and was further phosphorylated by the PMA treatment in a PKC-βI/II-mediated manner. We examined the effects of the displacement of Ser residues (72/300/340/403/408/427) in CerK by alanine (Ala, A) on its activity and phosphorylation. Triple mutations (S340/408/427A), but not a single or double mutations (S340/408A), in CerK significantly decreased the formation of C1P. PMA-induced phosphorylation levels in S340/408A- and S340/408/427A-CerK were significantly and maximally reduced, respectively, but were similar in CerK with a single mutation and wild-type CerK. Ser residue mutations tested, including six mutations, did not affect PMA-induced decreases in C1P formation more than expected. Treatments with the protein phosphatase inhibitors, okadaic acid and cyclosporine A, decreased the formation of C1P. These results demonstrated that the activity of CerK was regulated in a phosphorylation-dependent manner in cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sphingolipids such as sphingomyelin and glycosphingolipids (GSLs) derived from glucosylceramide (GlcCer), in addition to cholesterol, accumulate in cells/neurons in Niemann-Pick disease type C (NPC). The activities of acid sphingomyelinase and lysosomal glucocerebrosidase (GCase), which degrade sphingomyelin and GlcCer, respectively, are down-regulated in NPC cells, however, changes in GlcCer synthase activity have not yet been elucidated. We herein demonstrated for the first time that GlcCer synthase activity for the fluorescent ceramide, 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-ceramide) increased in intact NPC1((-/-)) cells and cell lysates without affecting the protein levels. In NBD-ceramide-labeled NPC1((-/-)) cells, NBD-fluorescence preferentially accumulated in the Golgi complex and vesicular specks in the cytoplasm 40 and 150 min, respectively, after labeling, while a treatment for 48 h with the GlcCer synthase inhibitors, N-butyldeoxynojirimycin (NB-DNJ) and 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, accelerated the appearance of vesicular specks emitting NBD-fluorescence within 40 min. The treatment of NPC1((-/-)) cells with NB-DNJ for 48 h additionally increased the levels of cholesterol, but not those of sphingomyelin. Increases in the activity of GlcCer synthase and formation of vesicular specks emitting NBD-fluorescence in NPC1((-/-)) cells were dependent on cholesterol. LacCer taken up by endocytosis, which accumulated in the Golgi complex in normal cells, accumulated in vesicular specks after 10 and 40 min in NPC1((-/-)) cells, and this response was not accelerated by the NB-DNJ treatment, but was restored by the depletion of cholesterol. The cellular roles for enhanced GlcCer synthesis and increased levels of cholesterol in the trafficking of NBD-ceramide metabolites in NPC1((-/-)) cells have been discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We report a patient with concealed Wolff-Parkinson-White syndrome who, following catheter ablation, demonstrated phase-3 and phase-4 retrograde block in a concealed accessory pathway. After an initial 'apparently successful' ablation, retrograde conduction was through the atrioventricular node during constant ventricular pacing. Ventricular extrastimulus testing was performed at a basic drive cycle length of 600 ms. Unexpectedly, ventricular extrastimuli at coupling intervals of 440-380 ms were conducted retrogradely over an accessory pathway, consistent with a phase-3 and phase-4 retrograde block in the accessory pathway. Residual accessory pathway conduction was eliminated in a single ablation session.

The typical fourth criterion for transient entrainment is defined when both a sudden shortening in conduction interval to and a distinct change in electrogram morphology at a bipolar recording site are demonstrated while performing overdrive pacing of a reentrant tachycardia from a single pacing site at two different constant rates. The purpose of this article was to test the hypothesis that if an intracardiac recording site showing both orthodromic and antidromic capture with entrainment pacing is located suitably distant from the circuit, sudden shortening in conduction interval to that site may occur without any significant change in the bipolar electrogram morphology (i.e., atypical form of the fourth criterion). Atrial overdrive pacing of orthodromic tachycardia was performed in 20 patients with either left anterior (12 patients) or left posterior (8 patients) accessory pathways. We investigated the effects of overdrive pacing from the proximal or distal coronary sinus, specifically effects on the electrogram interval and the electrogram morphology at the right atrial appendage. Overdrive pacing of orthodromic tachycardia from the proximal coronary sinus was performed in 10 of the 12 patients with left anterior accessory pathways; those 10 patients demonstrated the first entrainment criterion at the right atrial appendage site. Overdrive pacing of orthodromic tachycardia at still shorter cycle lengths demonstrated a sudden shortening in conduction interval to the right atrial appendage site. Despite shortening in conduction interval the morphology of the right atrial appendage electrogram was completely or almost identical to that during orthodromic tachycardia, indicating an atypical form of the fourth criterion. This criterion was not demonstrated in patients with left posterior accessory pathways. Thus, atypical fourth entrainment criterion was demonstrated during overdrive pacing of orthodromic tachycardia from the proximal coronary sinus only in patients with left anterior accessory pathways. Demonstration of atypical fourth criterion seems largely dependent on the location of the accessory pathway, the pacing, and the recording sites.

During retrograde conduction through an accessory pathway (AP) or the atrioventricular (AV) node, earlier activation of the distal recording site than a more proximal site of the coronary sinus (CS) generally indicates retrograde conduction via a distally located AP. Thus, after successful ablation of a left-sided AP, if the distal CS recording site is activated earlier than a more proximal site retrogradely, it is considered to suggest-in the absence of His-bundle recording or more frequently in the setting of poor recording of the low septal right atrial electrogram-a conduction via a second AP (located more distally), and not conduction via the AV node. Yet, we hypothesized that retrograde conduction through the AV node may activate the far distal site of the CS (CSD) earlier than a more proximal site, as the anterior atrial wavefront, coming retrogradely from the AV node and traveling along the anterior mitral annulus, could reach the CSD earlier than a more proximal site. To test this we studied 18 patients with intact retrograde conduction via the AV node, but without evidence of an AP. The CSD was recorded by means of a quadripolar catheter (interelectrode distance of 2-5 mm); retrograde activation sequence at the distal (CSD1-2) versus proximal (CSD3-4) bipolar recording site was determined during ventricular stimulation. In 12 of 18 patients the CSD1-2 recording site was activated 5-10 ms earlier than the CSD3-4 recording site, in 3 of 18 patients the CSD1-2 site was activated 5 ms later than the CSD3-4 site; in the remaining 3 patients both recording sites were depolarized simultaneously. The results indicate that the CSD was often depolarized earlier than a more proximal site by impulses that conducted to the atria retrogradely via the AV node while the quadripolar recording catheter was placed at the CSD. This observation, although not well documented previously, suggests that the sequence of retrograde atrial activation in the CS should be studied carefully in consideration of the actual location of the mapping catheter in order to correctly diagnose the presence or absence of conduction via an AP.

The present study was conducted with a sample of junior medical students at Jefferson Medical College to investigate the factors that influence students' overall satisfaction with the otolaryngology clerkship. The most important factor related to their overall satisfaction in the clerkship was their experience with residents, followed by experience with attending physicians, quality of rounds, and of lectures. The number of patients the students encountered, and number of rounds and lectures were deemed less important. Based on these findings, the authors of this paper concluded that the residents' role in teaching should be emphasized and students' satisfaction with the otolaryngology clerkship may be enhanced by developing residents' skills in teaching students.

Pause neurons (PNs), found in the pontine raphe nuclei, are important in the regulation of fast eye movements. The present study focuses on transmitters regulating the activity of the PNs. Extracellular spikes of single PNs and ocular motor nerve discharges were simultaneously recorded during horizontal vestibular nystagmus in the alert cat. Several transmitter candidates were iontophoretically applied, while methysergide, a serotonin antagonist, was administered both systemically and topically. The following data supported the conclusion that PNs are probably under the control of two different types of neurons, and the firing of PNs may be caused partly by GABAergic, but not by glycinergic neurons: 1) serotonin markedly decreased the spontaneous firing of the PNs; 2) methysergide abolished the inhibitory effect of serotonin on the PN firing; however, a pause pattern was maintained under this condition; 3) GABA moderately suppressed the firing but only in 25% of PNs; and 4) glycine hardly changed the PN firing in any case examined.

The efficacy of the frequency-selective auditory brain-stem response (ABR) in new borns and infants was assessed using an auditory stimulus of a 1-kHz tone pip and compared with the results of click-evoked ABR. In subjects whose responses to conventional behavioral audiometry were obtained at intensities of 40 to 70 dB, the ABR thresholds evoked by 1-kHz tone pips and clicks lay between 5 and 20 dB hearing threshold level (HTL). In subjects who did not respond to conventional behavioral audiometry at the intensity of 70 dB, ABR thresholds in each auditory stimulus were elevated by 35 to 70 dB HTL, and no responses were noted at 80 to 90 dB HTL. These results indicate that frequency-selective ABR can be applied clinically as an objective method of audiometry for newborns and infants.