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Background: Subclavian artery stenosis is generally screened by a left-right brachial systolic blood pressure difference. However, subclavian artery stenoses are often underdiagnosed due to marginally identified symptoms. In dialysis patients, a relative or absolute contradiction of measuring blood pressure in shunt brachial artery may further limit the disease screening., Case Summary: A 77-year-old female requiring dialysis presented with a suspected acute coronary syndrome complicated by cardiogenic shock. Five months before presentation, the patient was increasingly given inotropic drugs and had often chest discomfort during dialysis. An emergency coronary angiogram of the right coronary artery revealed 99% stenosis with hypoplasia. During catheterization, angiography of the aortic arch showed subtotal occlusion of the left subclavian artery. After revascularization, patients did not suffer from low blood pressure during haemodialysis., Discussion: Dialysis patients may have high perceived risk of subclavian artery stenosis. However, limitation of measuring blood pressure in shunt artery may enhance its underdiagnosis. Our case highlights the importance of screening for subclavian artery stenosis in patients undergoing dialysis., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Context: Attention-Deficit/Hyperactivity Disorder (ADHD) has been speculated to prolong concussion recovery; however, the evidence regarding concussion recovery for individuals with ADHD is limited., Objective: To examine the concussion recovery time based on ADHD status, sex, and age., Design: Cross-Sectional Study., Setting: High school., Participants: 935 (female n=382, 40.1%) concussions including 78 (female n=13, 20.0%) self-identified ADHD data were analyzed., Main Outcome Measures: A Poisson regression was utilized to estimate the Return- to-Learn (RTL) and Return-to-Sport (RTS) recovery outcomes with three predicting variables: ADHD status, sex, and age., Results: The mean RTL days of the ADHD and non-ADHD groups were 12.86 ± 10.89 (Median 11.0; IQR=8; 7.0-15.25) and 1.43 ± 8.39 (Median 9.0; IQR=9.0; 6.0-14.0), respectively. The mean RTS days of the ADHD and non-ADHD groups were 20.82 ± 15.25 days (Median 17.0; IQR=9; 12.0-21.0) and 18.03 ± 11.42 days (Median 15.0; IQR=10.0; 11.0-21.0), respectively. For RTL, the ADHD status (RR=1.16, 95%CI:1.08, 1.24, p<.001) and female sex (RR=1.13, 95%CI: 1.08, 1.17, p<.001) were significant variables for longer recovery, while the age was not (RR=0.995, 95%CI: 0.98, 1.01, p=.056). For RTS, the ADHD status (RR=1.17, 95%CI:1.12,1.23, p<.001), female sex (RR=1.07, 95%CI:1.04, 1.11, p<.001), and younger age (RR=0.98, 95%CI:0.96, 0.99, p<.001) were all significant variables for longer recovery., Conclusions: Healthcare providers must be aware of the elevated risk of prolonged concussion recovery among high school athletes with ADHD.

Background: Statins bring favourable effects on the clinical prognosis of patients with atherosclerotic disease partly through their anti-inflammatory properties. However, this effect has not been fully verified in patients with peripheral arterial disease (PAD). We aimed to test whether statins exert different prognostic effects depending on the degrees of inflammation in patients with PAD., Methods: This study was a sub-analysis of a multicenter prospective cohort of 2321 consecutive patients with PAD who received endovascular therapy (EVT). After excluding patients without information on C-reactive protein (CRP) levels at the time of index EVT, 1974 patients (1021 statin users and 953 non-users) were classified into four groups depending on CRP levels: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1-0.3 mg/dL), intermediate-high CRP (0.3-1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death, stroke, myocardial infarction, and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category., Results: During the median observation period of 316 days, the primary composite endpoint occurred in 112 (11.0 %) statin users and 178 (18.7 %) non-users (log-rank test, p  < 0.001). However, statin therapy was associated with significantly lower event rates only in the intermediate-high- and high-CRP categories ( p  = 0.02 and p  = 0.008, respectively). Multivariable Cox regression analysis revealed that statin use was independently associated with the primary endpoint only in the high-CRP category (adjusted hazard ratio: 0.64 [95 % confidence interval: 0.41-0.98])., Conclusion: Statins may exert favourable prognostic effects in patients with PAD and highly elevated CRP levels., Competing Interests: 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., (© 2024 The Authors.)

Background: The short-term mortality associated with veno-arterial extracorporeal membrane oxygenation combined with the Impella device (termed ECPELLA) for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) remains unclear., Methods and Results: The Japanese Registry for Percutaneous Ventricular Assist Devices (J-PVAD) includes data on all patients treated with an Impella in Japan. We extracted data for 922 AMI-CS patients who underwent ECPELLA support and conducted an exploratory analysis focusing on 30-day mortality. The median age of patients was 69 years, and 83.8% were male. The overall 30-day mortality was 46.1%. Factors associated with mortality included age >80 years, in-hospital cardiac arrest, systolic blood pressure <90 mmHg, serum creatinine >1.5 mg/dL, and serum lactate >4.0 mmol/L. In patients aged >80 years with any of these factors, mortality was significantly higher than in those without, ranging from 57.5% to 64.9%. The J-PVAD score assigns 1 point per predictor, with a C-statistic of 0.620 (95% confidence interval 0.586-0.654). The 30-day mortality was 20.0% for a J-PVAD score of 0, increasing to 70.0% for a score of 5., Conclusions: The J-PVAD data indicate high short-term mortality in AMI-CS patients treated with ECPELLA, particularly among older patients. Further studies are needed to validate this risk stratification in this patient subset.

Background: Multi-parametric assessment, including heart sounds in addition to conventional parameters, may enhance the efficacy of noninvasive telemonitoring for heart failure (HF). We sought to assess the feasibility of self-telemonitoring with multiple devices including a handheld heart sound recorder and its association with clinical events in patients with HF., Methods: Ambulatory HF patients recorded their own heart sounds, mono‑lead electrocardiograms, oxygen saturation, body weight, and vital signs using multiple devices every morning for six months., Results: In the 77 patients enrolled (63 ± 13 years old, 84 % male), daily measurements were feasible with a self-measurement rate of >70 % of days in 75 % of patients. Younger age and higher Minnesota Living with Heart Failure Questionnaire scores were independently associated with lower adherence (p = 0.002 and 0.027, respectively). A usability questionnaire showed that 87 % of patients felt self-telemonitoring was helpful, and 96 % could use the devices without routine cohabitant support. Six patients experienced ten HF events of re-hospitalization and/or unplanned hospital visits due to HF. In patients who experienced HF events, a significant increase in heart rate and diastolic blood pressure and a decrease in the time interval from Q wave onset to the second heart sound were observed 7 days before the events compared with those without HF events., Conclusions: Self-telemonitoring with multiple devices including a handheld heart sound recorder was feasible even in elderly patients with HF. This intervention may confer a sense of relief to patients and enable monitoring of physiological parameters that could be valuable in detecting the deterioration of HF., Competing Interests: Declaration of competing interest NK, TK, and HD are affiliated with a department endowed by Philips, Fukuda Denshi, KYOCERA, InterReha, and AMI Inc. based on collaborative research. NK receives an honorarium from Novartis Japan and research grants from AMI Inc. and EchoNous Inc. outside this work. NY and NM are employees of Asahi Kasei Corporation. TY is an employee of Philips Japan. KI has received research grant from Roche Diagnostics, SB Bioscience Co., Ltd., Fujirebio Inc., Bayel Sysmex, and Kanto Chemical Co. Inc. outside this work. YM received honoraria from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The main cause of acute coronary syndrome (ACS) is plaque rupture and thrombus formation. However, it has not been fairly successful to identify vulnerable plaque to rupture using conventional parameters of intravascular imaging modalities. Fractal analysis is one of the mathematical models to examine geometrical features of picture image using a specific parameter called as fractal dimension (FD) which suggests geometric complexity of the image. This study examined FD of the optical coherence tomography (OCT)-derived images of the culprit plaque in patients with ACS vs stable angina pectoris (SAP) to evaluate the feasibility of FD for identifying vulnerable coronary plaques prone to provoke ACS distinguished from stable plaques only provoking SAP. We examined 65 cases (34 ACS patients, 31 SAP patients) in which the culprit lesion was imaged by OCT before percutaneous coronary intervention in patients with ACS and SAP. The culprit plaque lesion in the ACS group had a significantly larger mean lipid arc (203.8 ± 39.4° vs 152.3 ± 34.5°, p < 0.001) and a larger lipid plaque length (12.6 ± 5.1 mm vs 7.7 ± 2.7 mm, p < 0.001) and a thinner fibrous cap thickness (75.3 ± 22.3 μm vs 134.8 ± 53.2 μm, p < 0.001) than those in the SAP group. The prevalence of OCT-derived macrophage infiltration (Mph) in the entire culprit coronary vessel as well as that of the OCT-derived thin-cap fibroatheroma (TCFA) at the culprit lesion were significantly greater in the ACS group than those in the SAP group, respectively (Mph: 61.8% vs 35.5%, p = 0.048; TCFA: 44.1% vs 6.4%, p < 0.001). The FD of culprit plaque in the ACS group was significantly greater than in the SAP group (2.401 ± 0.073 vs 2.341 ± 0.051, p < 0.001). In multivariate regression analysis, the presence of Mph was a significant determinant of FD (regression coefficient estimate 0.049, CI 0.018-0.079, p = 0.002). The FD of OCT-derived image of culprit coronary plaque in the ACS group was significantly greater than that in the SAP group, indicating that the culprit plaque in ACS were structurally more complex. Therefore, fractal analysis of coronary OCT images might be clinically useful for identifying coronary plaques prone to provoke ACS., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Background: Bleeding events are one of the major concerns in patients using oral anticoagulants (OACs). We aimed to evaluate the association between major bleeding and long-term clinical outcomes in atrial fibrillation (AF) patients taking OACs., Methods: We analyzed a database comprising two large-scale prospective registries of patients with documented AF: the RAFFINE and SAKURA registries. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, ischemic stroke, and myocardial infarction. Major bleeding was defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis. Cox multivariate analysis was used to determine the impact of major bleeding on the incidence of MACCE., Results: The median follow-up period was 39.7 (interquartile range, 33.1-48.1) months. Among 6,633 patients with AF who were taking OAC, 298 (4.5%) had major bleeding and 737 (11.1%) had MACCE. The incidence of MACCE was higher in patients with bleeding than in those without (18.33 and 3.22, respectively, per 100 patient-years; log-rank p < 0.0001). Multivariate logistic regression analysis revealed older age, vitamin K antagonist use, and antiplatelet drug use as independent predictors of major bleeding. Median duration of MACCE occurrence after major bleeding was 41 (interquartile range, 3-300) days. Multivariate Cox hazard regression analysis showed that the risk of MACCE was significantly higher in patients with major bleeding compared to those without (hazard risk, 4.64; 95% confidence interval, 3.62-5.94; p < 0.0001)., Conclusions: Major bleeding was associated with long-term adverse cardiovascular events among AF patients taking OAC. Therefore, reducing the risk of bleeding is important for improving clinical outcomes in patients with AF., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

The optimal timing for electrical cardioversion (ECV) in acute decompensated heart failure (ADHF) with atrial arrhythmias (AAs) is unknown. Here, we retrospectively evaluated the impact of ECV timing on SR maintenance, hospitalization duration, and cardiac function in patients with ADHF and AAs. Between October 2017 and December 2022, ECV was attempted in 73 patients (62 with atrial fibrillation and 11 with atrial flutter). Patients were classified into two groups based on the median number of days from hospitalization to ECV, as follows: early ECV (within 8 days, n = 38) and delayed ECV (9 days or more, n = 35). The primary endpoint was very short-term and short-term ECV failure (unsuccessful cardioversion and AA recurrence during hospitalization and within one month after ECV). Secondary endpoints included (1) acute ECV success, (2) ECVs attempted, (3) periprocedural complications, (4) transthoracic echocardiographic parameter changes within two months following successful ECV, and (5) hospitalization duration. ECV successfully restored SR in 62 of 73 patients (85%), with 10 (14%) requiring multiple ECV attempts (≥ 3), and periprocedural complications occurring in six (8%). Very short-term and short-term ECV failure occurred without between-group differences (51% vs. 63%, P = 0.87 and 61% vs. 72%, P = 0.43, respectively). Among 37 patients who underwent echocardiography before and after ECV success, the left ventricular ejection fraction (LVEF) significantly increased (38% [31-52] to 51% [39-63], P = 0.008) between admission and follow-up. Additionally, hospital stay length was shorter in the early ECV group than in the delayed ECV group (14 days [12-21] vs. 17 days [15-26], P < 0.001). Hospital stay duration was also correlated with days from admission to ECV (Spearman's ρ = 0.47, P < 0.001). In clinical practice, early ECV was associated with a shortened hospitalization duration and significantly increased LVEF in patients with ADHF and AAs., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Stent fracture is one of the complications of drug-eluting stent implantation. An 84-year-old man underwent coronary angiography for unstable angina. He had diffuse severe stenosis and calcified plaque in the left anterior descending artery and underwent percutaneous coronary intervention (PCI) in the left anterior descending artery for severe stenosis with chest pain. Thereafter, two subsequent stent fractures occurred, so the patient underwent another PCI to cover them. However, a stent fracture was found again one year later. The patient was asymptomatic and PCI was avoided due to the risk of further stent fracture. When a stent fracture occurs, it is important to provide appropriate treatment according to the anatomical findings of the vessel, symptoms and the presence of ischemia., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose Infant vision assessment often relies on grating acuity; however, its objectivity and convenience must be improved. A calibration-free eye-tracking system, even in preverbal children, enables easy and precise gaze analysis. This pilot study aimed to develop a reliable automated monocular vision screening. Methods Participants (n=118) underwent a grating visual acuity test using the eye-tracking system. Correlations between the grating acuity, uncorrected visual acuity, and refractive error were analyzed across different cutoff values of fixation duration percentage. Results Strong correlations were found between the grating acuity and refractive error at 69% and 88% thresholds. Similar correlations with uncorrected visual acuity were noted at 70% and 89% thresholds. False-negatives around the 70% threshold were noted, indicating potential overestimation of acuity in cases of low visual acuity/high refractive error. Discussion The results highlight the feasibility of calibration-free eye-tracking system-based monocular vision screening with an optimal screening threshold of 90%., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Niigata University of Health and Welfare issued approval 18627-210528. This study adhered to the tenets of the Declaration of Helsinki. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Noriaki Murata declare(s) a grant from Japan Society for the Promotion of Science. This work was supported by the JSPS KAKENHI (grant numbers: J21H00847, 23K18408, and 24K00402). Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Murata et al.)

Objective: To determine how football head impacts are influenced by self-efficacy (SE), helmetless tackling intervention participation (IP), and years of experience (YE) playing football., Design: Cross-sectional., Setting: Three high schools., Participants: 120 (male; n = 118, female; n = 2, 15.57 ± 1.23 years) participants were recruited from 5 high school teams (3 varsity and 2 junior-varsity)., Independent Variables: SE, days of IP, and YE playing tackle football., Main Outcome Measures: SE was measured using a 53-question survey and categorized into 5 subscales. The accumulation of total head impacts (THI) was measured using Riddell InSite Speedflex helmets (Elyria, OH) throughout the season. Head impact exposure (HIE) was standardized as a ratio of impacts per session (games, scrimmages, and practices). Multiple regression analyses tested the relationship between THI or HIE with the predictor variables., Results: For THI, 22.1% was explained by the predictors (r = 0.470, r2 = 0.221). Intervention participation had a negative correlation (B = -4.480, P = 0.019), whereas confidence in performing proper tackling and blocking (SE1) (B = 3.133, P = 0.010) and >8 YE (B = 135.9, P = 0.009) positively correlated with THI. For HIE, 25.4% was explained by the predictors (r = 0.504, r2 = 0.254). Intervention participation negatively correlated (B = -0.077, P = 0.007), whereas SE1 (B = 3.133, P = 0.010) and >8 YE (B = 2.735, P ≤ 0.001) correlated positively with HIE., Conclusions: Increased head impacts were associated with less helmetless tackling participation, more than 8 YE, and more self-confidence in tackling ability. Increasing the amount of time athletes spend practicing proper tackling and blocking techniques to reduce head first and risky play is warranted to reduce the amount of head impacts received over time., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

DesC1 and DesC2, which are fatty acid desaturases found in cyanobacteria, are responsible for introducing a double bond at the Δ9 position of fatty-acyl chains, which are subsequently esterified to the sn-1 and sn-2 positions of the glycerol moiety, respectively. However, since the discovery of these two desaturases in the Antarctic cyanobacterium Nostoc sp. SO-36, no further research has been reported. This study presents a comprehensive characterization of DesC1 and DesC2 through targeted mutagenesis and transformation using two cyanobacteria strains: Anabaena sp. PCC 7120, comprising both desaturases, and Synechocystis sp. PCC 6803, containing a single Δ9 desaturase (hereafter referred to as DesCs) sharing similarity with DesC1 in amino acid sequence. The results suggested that both DesC1 and DesC2 were essential in Anabaena sp. PCC 7120 and that DesC1, but not DesC2, complemented DesCs in Synechocystis sp. PCC 6803. In addition, DesC2 from Anabaena sp. PCC 7120 desaturated fatty acids esterified to the sn-2 position of the glycerol moiety in Synechocystis sp. PCC 6803., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pancreatic β-cell mass is a critical determinant of insulin secretion. Severe endoplasmic reticulum (ER) stress causes β-cell apoptosis; however, the mechanisms of progression and suppression are not yet fully understood. Here, we report that the autocrine/paracrine function of insulin reduces ER stress-induced β-cell apoptosis. Insulin reduced the ER-stress inducer tunicamycin- and thapsigargin-induced cell viability loss due to apoptosis in INS-1 β-cells. Moreover, the effect of insulin was greater than that of insulin-like growth factor-1 at physiologically relevant concentrations. Insulin did not attenuate the ER stress-induced increase in unfolded protein response genes. ER stress did not induce cytochrome c release from mitochondria. Mitochondrial hyperpolarization was induced by ER stress and prevented by insulin. The protonophore/mitochondrial oxidative phosphorylation uncoupler, but not the antioxidants N-acetylcysteine and α-tocopherol, exhibited potential cytoprotection during ER stress. Both procaspase-12 and cleaved caspase-12 levels increased under ER stress. The caspase-12 inhibitor Z-ATAD-FMK decreased ER stress-induced apoptosis. Caspase-12 overexpression reduced cell viability, which was diminished in the presence of insulin. Insulin decreased caspase-12 levels at the post-translational stages. These results demonstrate that insulin protects against ER stress-induced β-cell apoptosis in this cell line. Furthermore, mitochondrial hyperpolarization and increased caspase-12 levels are involved in ER stress-induced and insulin-suppressed β-cell apoptosis., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objectives: This study aimed to investigate the current use and impact of pulmonary artery catheters (PACs) in patients with cardiogenic shock (CS) who underwent Impella support., Design: This was a prospective multicenter observational study between January 2020 and December 2021 that registered all patients with drug-refractory acute heart failure and in whom the placement of an Impella 2.5, CP, or 5.0 pump was attempted or successful in Japan., Setting: Cardiac ICUs in Japan., Patients: Between January 2020 and December 2021, a total of 3112 patients treated with an Impella were prospectively enrolled in the Japan registry for percutaneous ventricular assist device (J-PVAD). Among them, 2063 patients with CS were divided into two groups according to the PAC use., Interventions: None., Measurements and Main Results: The primary endpoint was the 30-day mortality, and the secondary endpoints were hemolysis, acute kidney injury, sepsis, major bleeding unrelated to the Impella, and ventricular arrhythmias within 30 days. PACs were used in 1358 patients (65.8%) who underwent an Impella implantation. The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) was significantly higher in the patients with PACs than in those without. Factors associated with PAC use were the prevalence of hypertension, out-of-hospital cardiac arrest, New York Heart Association classification IV, the lesser prevalence of a heart rate less than 50, and the use of any catecholamine. The primary and secondary endpoints did not significantly differ according to the PAC use. Focusing on the patients with VA-ECMO use, the 30-day mortality and hemolysis were univariately lower in the patients with PACs., Conclusions: The J-PVAD findings indicated that PAC use did not have a significant impact on the short-term outcomes in CS patients undergoing Impella support. Further prospective studies are required to explore the clinical implications of PAC-guided intensive treatment strategies in these patients., Competing Interests: Dr. Okumura received funding from the Japan Abiomed Post-Market Surveillance Program. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: This post hoc subanalysis aimed to investigate the impact of polyvascular disease (PolyVD) in patients with acute myocardial infarction (AMI) in the contemporary era of percutaneous coronary intervention (PCI)., Methods and results: The Japan Acute Myocardial Infarction Registry (JAMIR), a multicenter prospective registry, enrolled 3,411 patients with AMI between December 2015 and May 2017. Patients were classified according to complications of a prior stroke and/or peripheral artery disease into an AMI-only group (involvement of 1 vascular bed [1-bed group]; n=2,980), PolyVD with one of the complications (2-bed group; n=383), and PolyVD with both complications (3-bed group; n=48). The primary endpoint was all-cause death. Secondary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major bleeding. In the 1-, 2-, and 3-bed groups, the cumulative incidence of all-cause death was 6.8%, 17.5%, and 23.7%, respectively (P<0.001); that of MACE was 7.4%, 16.4%, and 33.8% (P<0.001), respectively; and that of major bleeding was 4.8%, 10.0%, and 13.9% (P<0.001), respectively. PolyVD was independently associated with all-cause death (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.48-3.29), MACE (HR 2.07; 95% CI 1.40-3.07), and major bleeding (HR 1.68; 95% CI 1.04-2.71)., Conclusions: PolyVD was significantly associated with worse outcomes, including thrombotic and bleeding events, in the contemporary era of PCI in AMI patients.

Context: High school football remains a popular, physically demanding sport despite the known risks for acute brain and neck injury. Impacts to the head also raise concerns about their cumulative effects and long-term health consequences., Objective: To examine the effectiveness of a helmetless tackling training program to reduce head impact exposure in football participants., Design: A three-year, quasi-experimental, prospective cohort (clinicaltrials.gov #NCTXXX) study., Setting: Honolulu (XXX, XXX) area public and private secondary schools with varsity and junior varsity football., Patients or Other Participants: Football participants (n=496) ages 14 to 18 years old. Intervention(s) Participants wore new football helmets furnished with head impact sensor technology. Teams employed a season-long helmetless tackling and blocking intervention in Years 2 and 3 consisting of a 3-phase, systematic progression of 10 instructional drills., Main Outcome Measure(s): Head impact frequency per athlete exposure (ImpAE), location, and impact magnitude per participant intervention adherence levels (60% and 80%)., Results: An overall regression analysis revealed a significant negative association between ImpAE and adherence (p=0.003, beta=-1.21, SE=0.41). In year 3, a longitudinal data analysis of weekly ImpAE data resulted in an overall difference between the adherent and non-adherent groups (p=0.040 at 80%; p=0.004 at 60%), mainly due to decreases in top and side impacts. Mean cumulative impact burden for the adherent group (n=131: 2,105.84g ± 219.76,) was significantly (p=0.020) less than the non-adherent group (n=90: 3,158.25g ± 434.80) at the 60% adherence level., Conclusions: Participants adhering to the intervention on at least a 60% level experienced a 34% to 37% significant reduction in the number of head impacts (per exposure) through the season. These results provide additional evidence that a helmetless tackling and blocking training intervention (utilizing the HuTT® program) reduces head impact exposure in high school football players. Adherence to an intervention is crucial for achieving intended outcomes.

Background: Although there are many reports of temperature being associated with the onset of acute coronary syndrome (ACS), few studies have examined differences in ACS due to climatic differences between Japan and Thailand. The aim of this joint Japan-Thailand study was to compare patients with myocardial infarction in Japanese and Thai hospitals in different climates. Methods and Results: We estimated the climate data in 2021 for the Wakayama Prefecture and Chonburi Province, two medium-sized cities in Japan and Thailand, respectively, and ACS patients who were treated at the Wakayama Medical University (WMU) and Burapha University Hospital (BUH), the two main hospitals in these provinces (ACS patient numbers: WMU, n=177; BUH, n=93), respectively. In the Chonburi Province, although the average temperature was above 25℃, the number of ACS cases in BUH varied up to threefold between months (minimum: July, 4 cases; maximum: October, 14 cases). In Japan and Thailand, there was a mild to moderate negative correlation between temperature-atmospheric pressure at the onset of ACS, but different patterns for temperature-humidity (temperature-atmospheric pressure, temperature-humidity, and atmospheric pressure-humidity: correlation index; r=-0.561, 0.196, and -0.296 in WMU vs. r=-0.356, -0.606, and -0.502 in BUH). Conclusions: The present study suggests that other climatic conditions and factors, not just temperature, might be involved in the mechanism of ACS., Competing Interests: All authors report that they have no relationships relevant to the content of this paper., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Protein arginine methyltransferase 5 (PRMT5) is a well-known epigenetic regulatory enzyme. However, the role of PRMT5-mediated arginine methylation in gene transcription related to cardiac fibrosis is unknown. Here we show that fibroblast-specific deletion of PRMT5 significantly reduces pressure overload-induced cardiac fibrosis and improves cardiac dysfunction in male mice. Both the PRMT5-selective inhibitor EPZ015666 and knockdown of PRMT5 suppress α-smooth muscle actin (α-SMA) expression induced by transforming growth factor-β (TGF-β) in cultured cardiac fibroblasts. TGF-β stimulation promotes the recruitment of the PRMT5/Smad3 complex to the promoter site of α-SMA. It also increases PRMT5-mediated H3R2 symmetric dimethylation, and this increase is inhibited by Smad3 knockdown. TGF-β stimulation increases H3K4 tri-methylation mediated by the WDR5/MLL1 methyltransferase complex, which recognizes H3R2 dimethylation. Finally, treatment with EPZ015666 significantly improves pressure overload-induced cardiac fibrosis and dysfunction. These findings suggest that PRMT5 regulates TGF-β/Smad3-dependent fibrotic gene transcription, possibly through histone methylation crosstalk, and plays a critical role in cardiac fibrosis and dysfunction., (© 2024. The Author(s).)

Background: Nonobstructive general angioscopy (NOGA) can identify vulnerable plaques in the aortic lumen that serve as potential risk factors for cardiovascular events such as embolism. However, the association between computed tomography (CT) images and vulnerable plaques detected on NOGA remains unknown., Methods and Results: We investigated 101 patients (67±11 years; women, 13.8%) who underwent NOGA and contrast-enhanced CT before or after 90 days in our hospital. On CT images, the aortic wall thickness, aortic wall area (AWA), and AWA in the vascular area were measured at the thickest point from the 6th to the 12th thoracic vertebral levels. Furthermore, the association between these measurements and the presence or absence of NOGA-derived aortic plaque ruptures (PRs) at the same vertebral level was assessed. NOGA detected aortic PRs in the aortic lumens at 145 (22.1%) of the 656 vertebral levels. The presence of PRs was significantly associated with greater aortic wall thickness (3.3±1.7 mm versus 2.1±1.2 mm), AWA (1.33±0.68 cm 2 versus 0.89±0.49 cm 2 ), and AWA in the vascular area (23.2%±9.3% versus 17.2%±7.6%) ( P <0.001 for all) on the CT scans compared with the absence of PRs. The frequency of PRs significantly increased as the aortic wall thickness increased. Notably, a few NOGA-derived PRs were detected on CT in near-normal intima., Conclusions: The presence of NOGA-derived PRs was strongly associated with increased aortic wall thickness, AWA, and AWA in the vascular area, measured using CT. NOGA can detect PRs in the intima that appear almost normal on CT scans.

Background: The mechanism underlying a poor prognosis in patients with lower-extremity artery disease (LEAD) with heart failure is unknown. We examined the prognostic impact of the left ventricular ejection fraction (LVEF) in patients with LEAD who underwent endovascular therapy (EVT)., Methods and results: From August 2014 to August 2016, 2,180 patients with LEAD (mean age, 73.2 years; male, 71.9%) underwent EVT and were stratified into low-LVEF (LVEF <40%; n=234, 10.7%) and not-low LVEF groups. In the low- vs. not-low LVEF groups, there was a higher prevalence of heart failure (i.e., history of heart failure hospitalization or New York Heart Association functional class III or IV symptoms) (44.0% vs. 8.3%, respectively), diabetes mellitus, chronic kidney disease, below-the-knee lesion, critical limb ischemia, and incidence of major cardiovascular and cerebrovascular events (MACCEs) and major adverse limb events (MALEs) (P<0.001, all). Low LVEF independently predicted MACCEs (hazard ratio: 2.23, 95% confidence interval: 1.63-3.03; P<0.001) and MALEs (hazard ratio: 1.85, 95% confidence interval: 1.15-2.96; P=0.011), regardless of heart failure (P value for interaction: MACCEs: 0.27; MALEs: 0.52)., Conclusions: Low LVEF, but not symptomatic heart failure, increased the incidence of MACCEs and MALEs. Intensive cardiac dysfunction management may improve LEAD prognosis after EVT.

Introduction: In this study, we aimed to analyze the effectiveness of enhanced preventive measures against nosocomial COVID-19 Omicron outbreaks based on those encountered., Methods: We introduced PCR-based screening and syndromic surveillance, in addition to standard and transmission-based precautions, during a COVID-19 outbreak in three wards of Kagoshima University Hospital, a Japanese tertiary care hospital, in February 2022, amid the Omicron variant endemic. Furthermore, we analyzed the descriptive epidemiology and whole-genome sequencing (WGS) of positive SARS-CoV-2 PCR samples from this outbreak., Results: PCR-based screening tests were conducted following the identification of three cases through syndromic surveillance. As a result, 30 individuals tested positive for SARS-CoV-2, including 13 inpatients, five attendant family members, and 12 healthcare workers across the three wards. Notably, no new infections were observed within eight days following the implementation of preventive measures. Among the SARS-CoV-2 genomes analyzed (n = 16; 53.3%), all strains were identified as belonged to BA.1.1 variant. Detailed analysis of descriptive and molecular epidemiology, incorporating single-nucleotide polymorphism analysis of WGS and clarification of transmission links, considering two potential entry routes to the hospital., Conclusions: Introduction of additional preventive measures, including PCR-based screening and syndromic surveillance, in addition to WGS and descriptive epidemiology, is useful for the early intervention of nosocomial outbreaks and for revealing the transmission route of the COVID-19 Omicron variant., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Atrial fibrillation (AF) is an independent risk factor for stroke and systemic embolism. Cardiogenic and aortogenic emboli are causes of stroke or systemic embolism. Non-obstructive general angioscopy (NOGA) can be used to diagnose aortic intimal findings, including thrombi and atherosclerotic plaques, but little is known about NOGA-derived aortic intimal findings in patients with AF. This study focused on aortic intimal findings in patients with AF and evaluated the association between AF and aortic thrombi detected using NOGA. We enrolled 283 consecutive patients with coronary artery disease who underwent NOGA of the aorta between January 2017 and August 2022. Aortic intimal findings were screened using NOGA after coronary arteriography. The patients were divided into two groups according to their AF history (AF, n = 50 and non-AF, n = 233). Patients in the AF group were older than those in the non-AF group. Sex, body mass index, and coronary risk factors were not significantly different between the two groups. In the NOGA findings, the presence of intense yellow plaques and ruptured plaques was not significantly different between the two groups. Aortic thrombi were more frequent in the AF group than in the non-AF group (92.0 vs. 71.6%, p < 0.001). Multivariate logistic regression found that AF was independently associated with aortic thrombi (odds ratio 3.87 [95% CI 1.28-11.6], p = 0.016). The presence of aortic thrombi observed using NOGA was associated with AF in patients with coronary artery disease. The roles of aortic thrombi as well as cardiogenic embolism may require clarification., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown potential therapeutic benefits in heart failure (HF). However, data on their real-world usage and benefits in acute decompensated heart failure (ADHF) are limited., Methods and Results: We conducted a post hoc analysis of real-world data from 1108 patients with ADHF admitted to Nihon University Itabashi Hospital (Tokyo, Japan) between 2018 and 2022. Patients were divided into two groups based on the prescription of SGLT2 inhibitors during hospitalization: an SGLT2 inhibitor group (SGLT2i group) (n = 289) and a non-SGLT2i group (n = 819). The primary endpoints were death and rehospitalization for HF after discharge. The median age was 76 [interquartile range (IQR): 66, 83] years, and 732 patients (66%) were male. Data showed an increasing trend in the prescription of SGLT2 inhibitors since 2021. During a median follow-up period of 366 days (IQR: 116, 614), 458 (41.3%) patients reached the primary endpoint. The Kaplan-Meier analysis showed that the SGLT2i group had a significantly lower rate of composite events than the non-SGLT2i group, both overall (log-rank test, P < 0.001) and in the following left ventricular ejection fraction (LVEF) subgroups: HF with reduced ejection fraction (EF) (n = 413), HF with mildly reduced EF (n = 226), and HF with preserved EF (n = 466) (log-rank test; P = 0.044, P = 0.013, and P = 0.001, respectively). Furthermore, patients starting SGLT2 inhibitors during hospitalization had a significantly lower rate of composite events than those not using SGLT2 inhibitors (log-rank test, P < 0.001). This association was also significant in the LVEF subgroups (P = 0.005, P = 0.032, and P = 0.004, respectively)., Conclusions: The prescription and initiation of SGLT2 inhibitors during hospitalization are associated with improved post-discharge outcomes in patients with ADHF, irrespective of LVEF., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Empyema necessitans (EN) is a rare condition characterized by pleural infection with pus spreading into adjacent soft tissues. Although Mycobacterium tuberculosis and Actinomyces israelii are common causative agents, methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare, but it is associated with high mortality in empyema cases. We aimed to report a unique case of EN caused by MRSA and present a literature review to better understand this rare condition., Case Presentation: A 69-year-old man with a history of right ureteral stone presented with fever and left anterior thoracic pain. A physical examination revealed redness and swelling in the left thoracic region. Imaging studies confirmed EN with fluid accumulation around the sternocostal joint of the left first rib. MRSA was identified from blood and pleural fluid cultures. The patient received antimicrobial therapy, and a chest tube was inserted for drainage. Despite initial improvement, vertebral osteomyelitis was diagnosed on day 17. The antimicrobials were subsequently terminated after 6 weeks, but vertebral osteomyelitis recurred, and treatment was resumed and completed on day 215., Conclusion: EN caused by MRSA is rare, and the literature review revealed 14 cases from human sources. Positive blood cultures were observed in 40% of cases, and metastatic infections were present in 30% of cases. Osteomyelitis was the most common type of metastatic lesion. All the patients underwent drainage. Patients with MRSA-associated EN frequently develop disseminated lesions and should therefore be carefully examined. Moreover, appropriate treatment with antibiotics and drainage is necessary for a good prognosis. Although the prognosis appeared to be favorable in our review, publication bias and treatment challenges for metastatic infections should be considered., (© 2024. The Author(s).)

Background In Japan, effective educational methods to promote understanding of developmental disorders (DD) among young people have not been established, something that is necessary for an inclusive society. Aims This paper aimed to identify both the positive aspects and areas for improvement in a problem-solving program for middle and high school students on the topic of DD called inochi Gakusei Innovators Program (i-GIP). The study also sought to determine the changes in attitudes toward DD that occurred as a result of participating in the program. Method Semi-structured interviews were conducted online, with middle and high school students who participated in i-GIP, university students who helped manage the program, and cooperators with DD or their families. Inductive thematic analysis was conducted, and codes and themes were identified. Results Positive aspects of i-GIP included its project-based learning approach, raising awareness and understanding of developmental disorders, and the proactive attitude of the students. Areas for improvement in the program were identified, including program administration and addressing challenges related specifically to DD. Changes in attitudes and behavior toward DD were reported, along with improvements in interpersonal relationships. Conclusions and implications This study suggests that incorporating a project-based approach can be a useful manner to learn about DD among young people., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Murata et al.)

ABSTRACT In this study, Escherichia coli ( E. coli ) was used as an indicator bacterium treated with five different concentrations of chlorine (0.1; 0.5; 1.0; 2.0, and 5.0 mg/L) and without chlorine (0.0 mg/L) to evaluate the changes in the DOM characteristics. The dissolved organic carbon (DOC) concentration initially increased along with the chlorine concentrations and decreased after 24 h (0.0 and 0.1 mg/L) and 168 h (0.5; 1.0; 2.0 and 5.0 mg/L). Ultra-violet absorbance at 260 nm (UV 260 ) showed that the absorbance decreased for control without chlorine (0.0 mg/L) and 0.1 mg/L chlorine, while increased for other concentrations of chlorine within 120 h. The DOC and UV 260 results indicated that the high concentrations of chlorine initiated high contents of DOM which contained more humic-like molecules than the DOM released from E. coli without chlorine. Fluorescence excitation-emission matrix (EEM) analysis suggested that the DOM released from E. coli without chlorine enriched with protein-like substances, whereas the fulvic-like and humic-like substances more intensified in the DOM for the high concentrations of chlorine (>1.0 mg/L). The molecular weight distribution of DOM showed that the intensity of high molecular weight substances and polydispersity increased along with chlorine concentration and contact time, whereas the low molecular weight substances were relatively higher in the DOM for control without chlorine. The obtained results of this study would be useful for a better understanding of the variation of DOM during treatment and could be used as an important reference for optimizing the operation condition of the water treatment plants.

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA's F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600  ms - 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes - B1, provided by the Japanese space agency, JAXA, and B2 - that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission's science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2024.)

Concussions are caused by physical trauma to the head, face, or neck and can be sustained while surfing, increasing the risk of drowning. The purpose of this pilot study was to establish a preliminary assessment of concussion knowledge in a group of adult recreational surfers. Using the standardized Concussion Knowledge Index, an anonymous survey was conducted with 55 surfers. The Concussion Knowledge Index and similar statistical measures were used in a previous study of adult soccer players in England. Data from these 2 groups were compared. The preliminary data suggests that the group of adult surfers demonstrate more concussion knowledge than the group of adult soccer players. Further study into surfers' knowledge of concussion with a larger sample size could increase the clinical utility and generalizability of this study., Competing Interests: None of the authors identify a conflict of interest., (©Copyright 2023 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Background: Balloon pulmonary angioplasty (BPA) is an effective treatment for inoperable chronic thromboembolic pulmonary hypertension, with good results reported for residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). However, BPA is associated with complications, such as pulmonary artery perforation and vascular injury, which can lead to critical pulmonary hemorrhage requiring embolization and mechanical ventilation. Furthermore, the risk factors for occurrence of complications in BPA are unclear; therefore, this study aimed to evaluate predictors of procedural complications in BPA., Methods: In this retrospective study, we collected clinical data (patient characteristics, details of medical therapy, hemodynamic parameters, and details of the BPA procedure) from 321 consecutive sessions involving 81 patients who underwent BPA. Procedural complications were evaluated as endpoints., Results: BPA for residual PH after PEA was performed in 141 sessions (43.9 %), which involved 37 patients. Procedural complications were observed in 79 sessions (24.6 %), including severe pulmonary hemorrhage requiring embolization in 29 sessions (9.0 % of all sessions). No patients experienced severe complications requiring intubation with mechanical ventilation or extracorporeal membrane oxygenation. Age ≥ 75 years and mean pulmonary artery pressure ≥ 30 mmHg were independent predictors of procedural complications. Residual PH after PEA was a significant predictor of severe pulmonary hemorrhage requiring embolization (adjusted odds ratio, 3.048; 95 % confidence interval, 1.042-8.914, p = 0.042)., Conclusions: Older age, high pulmonary artery pressure, and residual PH after PEA increase the risk of severe pulmonary hemorrhage requiring embolization in BPA., Competing Interests: Declaration of competing interest Ryosuke Ito, Jun Yamashita, Sayo Ikeda, Yuki Nakajima, Tomohiro Kasahara, Yuichi Sasaki, Lisa Takahashi, Ikki Komatsu, Naotaka Murata, and Taishiro Chikamori are affiliated with an endowed department sponsored by Abbott Medical Japan LLC. However, these authors and others disclose no conflicts of interest related to this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This study aimed to examine the clinical role of non-gated computed tomography (CT) in ruling out fatal chest pain in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), with a focus on the time of arrival at the hospital to coronary angiography (CAG) and peak creatine kinase (CK) levels., Methods: We retrospectively examined 196 NSTE-ACS patients who were admitted with urgently diagnosed NSTE-ACS and underwent percutaneous coronary intervention between March 2019 and October 2022. The patients were divided into three groups, namely, non-CT group, CT and defect- group, and CT and defect+ group, based on whether they underwent a CT scan and the presence or absence of perfusion defects on the CT image., Results: After the initial admission for NSTE-ACS, 40 patients (20.4%) underwent non-gated CT prior to CAG. Among these 40 patients, 27 had a perfusion defect on the CT scan. The incidence of contrast-induced nephropathy was not different among the three groups. The CT and defect+ group had a shorter arrival-to-CAG time than that of the non-CT group. In NSTE-ACS patients with elevated CK levels, the CT and defect+ group had lower peak CK levels than those in the non-CT group., Conclusion: NSTE-ACS patients with perfusion defects on non-gated CT had a shorter time from arrival to CAG, which might be associated with a lower peak CK. Non-gated CT might be useful for early diagnosis and early revascularization in the clinical setting of NSTE-ACS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Miyagawa, Arai, Takahashi, Nakajima, Migita, Mizobuchi, Tanaka, Fukumoto, Morikawa, Mineki, Kojima, Murata, Sudo and Okumura.)

The fractional flow reserve (FFR) cut-off values of 0.75 or 0.8 have been widely used; however, whether they apply to patients on hemodialysis remains unknown. We aimed to investigate the cut-off value of FFR associated with clinical outcomes in patients on hemodialysis. Using the Japanese multicenter registry, we analyzed data of patients on hemodialysis with measured FFR between January 2010 and December 2016. Survival classification and regression tree analysis for the composite primary outcome of cardiovascular mortality, myocardial infarction, and target vessel revascularization revealed a threshold FFR of 0.83. Multivariate Cox regression analyses were performed for the clinical outcomes. Additionally, the primary outcome was analyzed using propensity score matching by dividing the patients into complete and incomplete revascularization groups according to the presence of residual lesions with an FFR of ≤0.83 after the intervention. Of the 212 included patients, 112 (52.8%) had lesions with an FFR of ≤0.83. After adjusting for confounders, an FFR of ≤0.83 was associated with a higher risk for the primary outcome (adjusted hazard ratio 2.01, 95% confidence interval 1.11 to 3.66, p = 0.021). Propensity score matching showed that complete revascularization for lesions with an FFR of ≤0.83 was associated with a reduced risk for the primary outcome compared with incomplete revascularization (hazard ratio 0.38, 95% confidence interval 0.20 to 0.71, log-rank p = 0.0016). In conclusion, an FFR of ≤0.83 was an independent predictor of clinical events in patients on hemodialysis. Furthermore, complete revascularization was associated with better clinical outcomes. Thus, this population may require a distinct FFR cut-off value., Competing Interests: Declaration of Competing Interest Dr. Shiono receives lecture fees from Phillips Japan, Zeon Medical Inc., and Abbott Medical Japan. Dr. Kawase receives lecture fees from Phillips Japan, Zeon Medical Inc., Boston Scientific Corporation and Abbott Medical Japan. Dr. Yamashita is affiliated with an endowed department sponsored by Abbott Medical Japan and receives consultation fee and lecture fees from Kaneka Medix and Phillips Japan. Dr. Amano receives lecture fees from Astellas Pharma, Astra Zeneca, Bayer, Daiichi-Sankyo, and Bristol-Myers Squibb. Dr. Tanaka receives lecture fees from Abbott Medical Japan and Daiichi-Sankyo. Dr. Akasaka receives lecture fees from Abbott Medical Japan and is Medical Advisor of Terumo Corporation. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Non-alcoholic fatty liver disease (NAFLD) and acute myocardial infarction (AMI) have common pathological links. This study investigates the prognostic impact of NAFLD assessed as hepatic steatosis (HS) by computed tomography (CT) in AMI patients and explores the mechanistic role of NAFLD in cardiovascular (CV) events using coronary angioscopy (CAS)., Methods: We retrospectively examined 342 AMI patients who underwent CT followed by primary percutaneous coronary intervention (PCI) between January 2014 and December 2019. HS was defined as a hepatic to spleen attenuation ratio of <1.0 on CT scans. Major cardiac events (MCE) included cardiac death, non-fatal myocardial infarction, target-vessel revascularization, and target-lesion revascularization., Results: HS was identified in 88 patients (26 %). Patients with HS were significantly younger, had a higher body mass index, and higher hemoglobin A1c, triglyceride, and malondialdehyde low-density lipoprotein levels (all p < 0.05). MCE occurred more frequently [27 (30.7 %) vs. 39 (15.4 %), p = 0.001] in the HS group than in the non-HS group. In the multivariate analysis, the presence of HS was an independent predictor of MCE after adjusting for metabolic risk factor and liver function markers. Among the 74 patients who underwent CAS for a median of 15 days after primary PCI, 51 (69 %) had intrastent thrombus, which was strongly associated with the presence of HS [18 (35 %) vs. 1 (4 %), p = 0.005]., Conclusions: AMI patients with NAFLD detected by CT often had CAS-derived intrastent thrombi and were at a high risk for CV events. Therefore, these patients should be carefully monitored., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective Sodium-glucose co-transporter-2 inhibitors (SGLT2is), such as dapagliflozin, have a diuretic effect, and their early initiation to treat acute heart failure (AHF) may improve outcomes; however, the significance of the timing of starting dapagliflozin after hospital admission remains unclear. Methods We performed a post hoc analysis of a prospective, observational registry. Participants were divided into the early (E) group and late (L) group using the median time to the initiation of dapagliflozin (6 days) as the cut-off. We evaluated the relationship between the time to the initiation of dapagliflozin after hospital admission and patient characteristics and the length of the hospital stay. Patients Study subjects were 118 patients with AHF admitted between January 2021 and April 2022 who were started on dapagliflozin treatment (10 mg/day). Results Patients were divided into the E group (n=63) and L group (n=55). The HF severity as evaluated by the New York Heart Association class and the N-terminal pro-brain natriuretic peptide level was not significantly different between the groups. The time to the initiation of dapagliflozin and length of hospital stay showed a significant positive correlation (p<0.001, r=0.46). The hospital stay was significantly shorter in group E [median, 16.5 days; interquartile range (IQR): 13-22 days] than in group L (median, 22 days; IQR: 17-27 days; p=0.002). A multivariate logistic regression analysis showed that the early initiation of dapagliflozin was independently associated with a shorter hospital stay, even after multiple adjustments. Conclusion Early initiation of dapagliflozin after hospital admission is associated with a shorter hospital stay, suggesting it is a key factor for shortening hospital stays.

Drug overdose can lead to a range of symptoms, including potentially life-threatening cardiac arrhythmias. However, identifying the specific causative drug upon admission can be challenging in many cases. The toxidrome approach is a method that utilizes toxidromes, which are collections of findings obtained from physical examination and ancillary tests, that may be caused by a specific toxin. In this particular case, a man presented with an unknown drug overdose that caused symptoms indicative of anticholinergic effects and abnormal electrocardiogram (ECG) findings. The ECG revealed an R wave in lead aVR, S waves in leads I and aVL, and wide QRS tachycardia with a Brugada pattern. Shortly after arrival, the patient developed cardiac arrest due to a lethal arrhythmia. Prompt initiation of venoarterial extracorporeal cardiopulmonary membrane oxygenation (VA-ECMO) was performed. Fortunately, the patient achieved full neurological recovery, and the overdosed drug was identified as diphenhydramine. When diagnosing and treating drug overdose caused by an unidentified substance, diphenhydramine toxicity should be considered when an anticholinergic toxidrome is present and a Brugada pattern is observed on the ECG. VA-ECMO demonstrates potential as a viable treatment option when initial interventions prove ineffective., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Symptoms of lower-extremity artery disease (LEAD) emerge from impaired vascularization in distal circulation of the extremities. Calcium channel blockers (CCB) can improve distal circulation when used as adjunctive therapy with endovascular treatment (EVT), but few studies have evaluated that. We investigated the relationship between CCB therapy and post-EVT outcomes. Through a consecutive EVT registry, we evaluated those relationships in whole cohort and the following 2 subgroups; the patients suffered from intermittent claudication (IC) or chronic limb-threatening ischemia (CLTI), with adjusting baseline characteristics by propensity score matchings. The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE, a composite endpoint of all death, nonfatal myocardial infarction, and nonfatal stroke), and major adverse limb event (MALE, a composite of major amputation, acute limb ischemia, and surgical reintervention). The group that received CCB had less MALE in whole cohort (HR 0.31; 95% confidence interval (CI) 0.20-0.47), and less MACCE and MALE in CLTI cohort (HR 0.67; 0.50-0.89 and 0.32; 0.20-0.52 respectively) compared to the group that did not receive CCB. The relationships were common in the cohorts with baseline adjustment. MACCE and MALE in IC (HR 1.01; 0.57-1.80 and 0.60; 0.25-1.45, respectively) showed no significant differences both with and without baseline adjustment. CCB use was related to fewer MACCE and MALE events in adjusted patients who underwent EVT, and the trend was more evident, especially in the adjusted CLTI cohort. This study highlights the necessity of future studies regarding CCB. Clinical Trial Registration: URL: https://www.umin.ac.jp ; Unique identifiers: UMIN000015100., (© 2023. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Focusing on the differences in the catalytic properties of two type I fatty acid synthases FasA and FasB, the fasA gene was disrupted in an oleic acid-producing Corynebacterium glutamicum strain. The resulting oleic acid-requiring strain whose fatty acid synthesis depends only on FasB exhibited almost exclusive production (217 mg/L) of palmitic acid (C16:0) from 1% glucose under the conditions supplemented with the minimum concentration of sodium oleate for growth. Plasmid-mediated amplification of fasB led to a 1.47-fold increase in palmitic acid production (320 mg/L), while fasB disruption resulted in no fatty acid production, with excretion of malonic acid (30 mg/L). Next, aiming at conversion of the palmitic acid producer to a producer of palmitoleic acid (POA, C16:1Δ9), we introduced the Pseudomonas nitroreducens Δ9-desaturase genes desBC into the palmitic acid producer. Although this resulted in failure, we noticed the emergence of suppressor mutants that exhibited the oleic acid-non-requiring phenotype. Production experiments revealed that one such mutant M-1 undoubtedly produced POA (17 mg/L) together with palmitic acid (173 mg/L). Whole genomic analysis and subsequent genetic analysis identified the suppressor mutation of strain M-1 as a loss-of-function mutation for the DtxR protein, a global regulator of iron metabolism. Considering that DesBC are both iron-containing enzymes, we investigated the conditions for increased iron availability to improve the DesBC-dependent conversion ratio of palmitic acid to POA. Eventually, supplementation of both hemin and the iron chelator protocatechuic acid in the engineered strain dramatically enhanced POA production to 161 mg/L with a conversion ratio of 80.1%. Cellular fatty acid analysis revealed that the POA-producing cells were really equipped with unnatural membrane lipids comprised predominantly of palmitic acid (85.1% of total cellular fatty acids), followed by non-native POA (12.4%)., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Macroautophagy is a catabolic process that coordinates with lysosomes to degrade aggregation-prone proteins and damaged organelles. Loss of macroautophagy preferentially affects neuron viability and is associated with age-related neurodegeneration. We previously found that α-synuclein (α-syn) inhibits lysosomal function by blocking ykt6, a farnesyl-regulated soluble NSF attachment protein receptor (SNARE) protein that is essential for hydrolase trafficking in midbrain neurons. Using Parkinson's disease (PD) patient iPSC-derived midbrain cultures, we find that chronic, endogenous accumulation of α-syn directly inhibits autophagosome-lysosome fusion by impairing ykt6-SNAP-29 complexes. In wild-type (WT) cultures, ykt6 depletion caused a near-complete block of autophagic flux, highlighting its critical role for autophagy in human iPSC-derived neurons. In PD, macroautophagy impairment was associated with increased farnesyltransferase (FTase) activity, and FTase inhibitors restored macroautophagic flux through promoting active forms of ykt6 in human cultures, and male and female mice. Our findings indicate that ykt6 mediates cellular clearance by coordinating autophagic-lysosomal fusion and hydrolase trafficking, and that macroautophagy impairment in PD can be rescued by FTase inhibitors. SIGNIFICANCE STATEMENT The pathogenic mechanisms that lead to the death of neurons in Parkinson's disease (PD) and Dementia with Lewy bodies (LBD) are currently unknown. Furthermore, disease modifying treatments for these diseases do not exist. Our study indicates that a cellular clearance pathway termed autophagy is impaired in patient-derived culture models of PD and in vivo We identified a novel druggable target, a soluble NSF attachment protein receptor (SNARE) protein called ykt6, that rescues autophagy in vitro and in vivo upon blocking its farnesylation. Our work suggests that farnesyltransferase (FTase) inhibitors may be useful therapies for PD and DLB through enhancing autophagic-lysosomal clearance of aggregated proteins., (Copyright © 2023 the authors.)

The incidence of lower extremity artery disease (LEAD) in patient receiving hemodialysis is remarkably higher than the general population. The treatment strategy and prognosis for LEAD patients differs depending on whether a patient has intermittent claudication (IC) or critical limb-threatening ischemia (CLTI). However, the distinction between the prognosis in HD-dependent patients with IC and CLTI has not been fully elucidated. This study is to determine whether indication of PAD has a distinct impact on major adverse cardiovascular and cerebrovascular events (MACCE) and limb events in patients receiving hemodialysis. The current study included 2321 prospectively enrolled patients from the Tokyo taMA peripheral vascular intervention research ComraDE registry (UMIN-CTR no. UMIN000015100) between September 2014 and December 2016. Out of the enrolled patients, 1644 were not receiving hemodialysis (non-HD patients) and 603 were receiving hemodialysis (HD patients). A composite of all-cause death, myocardial infarction, and stroke events defined as MACCE; while limb events were defined as a composite of unscheduled major amputation, unscheduled major lower limb surgery, acute limb ischemia, unscheduled endovascular treatment, and target lesion revascularization. Propensity score matching was applied among the non-HD and HD patients, in whole group, IC subgroup, and CLTI subgroup. Kaplan-Meier analysis was used for the analysis of outcomes for the whole group, IC subgroup, and the CLTI subgroup. CLTI accounted for 75.5% of the HD patients, whereas IC was 63.4% in the non-HD patients. The HD patients exhibited more frequent below-the-knee lesions than those in the non-HD patients in both IC (p = 0.01) and CLTI (p < 0.001) subgroups. Overall, HD patients exhibited a significantly higher rate of MACCE at 24 months. This trend was similar for limb events in whole group and CLTI subgroup. In contrast, no significant differences in outcomes for limb events were found in IC subgroup. Although, prognosis after EVT in HD patients were significantly worse than non-HD patients, comparable outcome with non-HD patients was observed in the patients treated for IC. Clinical trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR No. UMIN000015100)., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Clinical practice guidelines assist healthcare professionals in providing evidence-based care. However, pharmaceutical companies' financial interests often influence guideline content. This study aimed to elucidate the magnitude of financial ties among Japanese gastroenterology guideline authors and the pharmaceutical industry., Methods: Using pharmaceutical company disclosed payment data, we evaluated financial conflicts of interest (COI) among Japanese Society of Gastroenterology guideline authors between 2016 and 2021. Additionally, we assessed the evidence quality supporting guideline recommendations and associations with financial COI. Finally, we evaluated author COI management during guideline development against global standards., Results: Overall, 88.2% (231/262) of guideline authors received a median of $12 968 (interquartile range [IQR]: $1839-$70 374) in payments between 2016 and 2019 for lectures, writings, and consulting. Chairpersons received significantly higher payments (median: $86 444 [IQR: $15 455-$165 679]). Notably, 41 (15.6%) authors had undeclared payments exceeding declaration requirements. Low or very low-quality evidence supported 41.0% of recommendations. There was a negative association between the median 4-year payment per author and the proportion of recommendations based on low-quality evidence (odds ratio: 0.966 [95% confidence interval [95% CI]: 0.945-0.987], P = 0.002) and positive association with moderate-quality evidence (odds ratio: 1.018 [95% CI: 1.011-1.025], P < 0.001). Still, the Japanese Society of Gastroenterology guideline development process remains less transparent, with insufficient COI policies relative to global standards., Conclusion: There were extensive financial COI between pharmaceutical companies and guideline authors, and more than 40% of recommendations were based on low-quality evidence. More rigorous and transparent COI policies for guideline development adhering to global standards are warranted., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)