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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.)

Objective: To examine the benefits of full-time hospital facility dogs (HFDs) working with qualified nurse handlers for inpatients in a pediatric medical facility., Methods: A questionnaire survey on the evaluation of HFD activities was conducted in a hospital that had introduced HFDs for the first time in Japan and has been using them for 9 years. Of the 626 full-time medical staff, 431 responded, of which 270 who observed HFD activities were included in the analysis. The Questionnaire contained 20 questions, and nine questions were selected for presentation in this paper because they focused on the situations in which HFD activities were thought to have a strong impact on inpatients. A comparison of the respondents' evaluations for each question was made, and differences in the respondents' attributes (such as profession, length of clinical experience and experience of dog ownership) for those items were examined., Results: The impact of HFDs in terminal care was ranked highest among the respondents. Similarly, HFDs increased patient cooperation for clinical procedures. The responses to these two items did not differ statistically depending on the respondents' attributes. The results imply that patients were more cooperative even for highly invasive examinations and procedures with the support of HFD activities., Conclusions: Healthcare providers considered that HFDs were useful, especially for providing support during the terminal phase and for gaining patients' cooperation for procedures. The fact that the handler was a nurse and the HFD team worked full-time may have enhanced the effectiveness of the program., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Murata-Kobayashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.)

Depression is a chronic illness that affects mood, physical health, and overall vitality and quality of life. Depression has been associated with an increased risk of all-cause and cardiovascular mortality among patients with peripheral arterial disease (PAD). Therefore, this study aimed to compare the incidence of depression before and after endovascular treatment in patients with lower limb PAD. This is an important clinical issue considering the worldwide increase in PAD with the aging population and the known negative impact of depression on recovery. This was a retrospective sub-analysis of data from the Tokyo Peripheral Vascular Intervention Study using the TOMA-CODE registry. The presence and extent of depressive symptoms were evaluated using the patient health questionnaire (PHQ-9), with a depressive tendency score of ≥ 5. The PHQ-9 score was evaluated before endovascular treatment (EVT) and at 4 (± 1) weeks after EVT. The study population consisted of 87 patients who completed the PHQ-9 before EVT, with 76 completing the post-EVT PHQ-9. Of these 76, 19 had a pre-EVT score ≥ 5. Overall, there was no difference in the pre- and post-EVT scores (P = 0.091). There was no significant change in the 19 patients with a pre-EVT score ≥ 5 (mean 9.2 ± 4.4); however, there was a tendency to improve in the pre- to post-EVT score (mean, 6.9 ± 5.2; P = 0.059). Diabetes was a significant negative factor for pre- to post-EVT score improvement (P = 0.023). Overall, symptoms of depression showed the tendency to improve at 30 days post-EVT. However, diabetes was associated with lower improvement in symptoms., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: While there is a discordance between fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) in some cases, the mechanisms underlying these discordances have not yet been fully clarified. We examined whether vascular damage as assessed by measurement of the brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, or ankle brachial pressure index (ABI), a marker of atherosclerotic arterial stenosis, might be associated with their discordances., Methods: FFR and NHPRs were measured in 283 consecutive patients (69 ± 10 years old). Based on previously established cut-off values of the two markers (i.e. +/- = FFR ≤/> 0.80 or =NHPRs ≤/> 0.89), the study participants were divided into four groups (the + and - signs denoting "predictive of significant stenosis" and "not predictive of significant stenosis," respectively): the FFR+/NHPRs+ group (n = 124), FFR-/NHPRs+ group (n = 16), FFR+/NHPRs- group(n = 65), and FFR-/NHPRs- group (n = 78). The baPWV and ABI were also measured in all the participants, and values of <2000 cm/s and ≥1.00 of the baPWV and ABI, respectively, were considered as representing relatively less advanced atherosclerotic systemic vascular damage., Results: The prevalence of subjects with ABI ≥1.00 was higher in the FFR+/NHPRs- group than in the FFR-/NHPRs- group (p < 0.05). When the study subjects were divided into 2 groups, namely, the FFR+/NHPRs- group and the combined group, the prevalence of ABI ≥1.00 and that of baPWV <2000 cm/s were higher in the FFR+/NHPRs- group as compared with those in the combined group (p < 0.05). The results of binary logistic regression analysis demonstrated that ABI ≥1.00 was associated with a significant odds ratio (2.34, p < 0.05) for the FFR+/NHPRs- discordance., Conclusion: The FFR+/NHPRs- discordance appears to be observed in patients with relatively less advanced atherosclerotic systemic vascular damage. Thus, ABI ≥1.00 may be a marker of the presence of the FFR+/NHPRs- discordance., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To verify the surgical results and risk factors for ab interno trabeculotomy using a Kahook Dual Blade (KDB-LOT) in patients with various glaucoma types., Methods: This study was a retrospective case series of 205 eyes that underwent KDB-LOT. For Kaplan-Meier survival analysis, criterion A was defined as a ≤ 20% reduction in intraocular pressure (IOP) from baseline. Criteria B, C, and D were IOPs of ≤ 21, 18, and 15 mmHg, respectively. The Cox proportional hazard (CPH) model investigated prognostic factors., Results: The mean (SD) IOP decreased from 24.7 (7.98) to 17.6 (4.80) mmHg in all cases, from 21.3 (6.88) to 17.8 (3.52) mmHg in primary open-angle glaucoma (POAG), from 25.4 (7.32) to 17.1 (4.65) mmHg in exfoliation glaucoma, from 30.6 (8.88) to 17.8 (8.29) mmHg in uveitic glaucoma, and from 30.8 (7.29) to 17.3 (0.83) mmHg in steroid-induced glaucoma at 1 year after KDB-LOT. The Kaplan-Meier survival analysis showed that patients with POAG had the best prognosis under criteria B and C, and the 1-year survival rate in patients under criterion D was less than 35% for any disease type. CPH analysis revealed that age and KDB-LOT with phacoemulsification were good prognostic factors. Risk factors for surgical failure were previous cataract surgery, selective laser trabeculoplasty, and postoperative peripheral anterior synechiae., Conclusion: KDB-LOT was effective in treating patients with several glaucoma types but showed difficulty in pushing IOP below 15 mmHg. Prognostic factors should be considered when making decisions regarding surgical indications., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We provide here an overview of the remarkable life and outstanding research of David (Dave) Charles Fork (March 4, 1929-December 13, 2021) in oxygenic photosynthesis. In the words of the late Jack Edgar Myers, he was a top 'photosynthetiker'. His research dealt with novel findings on light absorption, excitation energy distribution, and redistribution among the two photosystems, electron transfer, and their relation to dynamic membrane change as affected by environmental changes, especially temperature. David was an attentive listener and a creative designer of experiments and instruments, and he was also great fun to work with. He is remembered here by his family, coworkers, and friends from around the world including Australia, France, Germany, Japan, Sweden, Israel, and USA., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: With advances in medical technology, the number of children with medical complexity (CMC) has increased. Excursions with such children encourage their social participation and have been shown to have a positive impact on their caregivers. However, the first-hand experience of the excursions has not yet been evaluated regarding the difficulties faced by CMC and their caregivers during preparation, transportation, and in the local area., Methods: Semi-structured interviews were conducted with eight informal and eight formal caregivers of CMC who attended an excursion to Tokyo Disney Land (TDL) via video conference. We investigated challenges that they had experienced through the excursion, performing inductive thematic analysis., Results: Three themes were identified: the preparation stage (Theme 1), problems encountered while traveling to the theme park (Theme 2), and problems at the theme park (Theme 3). In the preparation stage, three subthemes, i.e. preparation for the trip, cooperation with related parties, and researching about the theme park and asking for help, are reported. Theme 2 includes four subthemes: activities of daily living, respiratory care, luggage, and weather changes. Theme 3 has three subthemes: activities of daily living, physical condition management, and issues for the theme parks., Conclusions: We found that securing the power supply, location, and time for daily procedures are challenges in realizing excursions for CMC, but with sufficient preparation, it is possible in Japan without major difficulty., (© 2022 Japan Pediatric Society.)

Introduction: An easy-to-access and effective psychotherapy for bereaved informal caregivers has not been established. People with higher self-compassion status tend to have lower bereavement related grief, psychotherapy focused on self-compassion can be promising for this population. This study aimed to examine the feasibility of online self-compassion focused psychotherapy for bereaved informal caregivers., Method and Analysis: A total of 60 study participants will undergo an intervention programme comprising online sessions of 2 hours per week for five consecutive weeks and undertake postsession work. The intervention personnel will comprise psychologists who have received more than 10 hours of structured training. The primary endpoint will be assessed on the intervention completion rate, with secondary endpoints consisting of the Complicated Grief Questionnaire, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7, Brief Resilience Scale and Self-Compassion Scale. Evaluations will be conducted preintervention, immediately after intervention, and 4 and 12 weeks after intervention., Ethics and Dissemination: This study has been reviewed and approved by the Ethics Committee of the Kyoto University Graduate School and Faculty of Medicine, Kyoto University Hospital, Japan (Approved ID: C1565). The results of this study will be disseminated through publication in a peer-reviewed journal and conference presentations., Trial Registration Number: UMIN000048554., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Negative pressure wound therapy( NPWT) is used primarily for tissue defects. In recent years, cardiovascular surgery via full sternotomy is increasingly performed through small incisions, but the rate of cardiovascular surgery through median sternotomy remains high in elderly patients, who frequently have complicated cardiovascular diseases. Mediastinitis, among other surgical site infections( SSIs), is a serious complication after cardiovascular surgery that must be resolved. Mediastinitis has a high mortality rate once it occurs, and cost of treatment and a negative impact on a patient are substantial. In some countries, NPWT is for the prophylaxis of mediastinitis, but only for cases with a significant risk of SSI. To avoid SSI, prophylactic NPWT is administered in all cardiovascular surgeries through median sternotomy at our hospital. Of 641 consecutive median sternotomy patients from March 2011 to March 2021, 601 cases were able to observe the wound for at least 30 days following the surgery. In the 601 cases, we found a statistically significant difference in the incidence of SSI. The results suggest that prophylactic NPWT significantly reduces SSI after cardiovascular surgery through median sternotomy.

Background: The effect of left subclavian artery tortuosity during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) remains unclear., Methods: Of 245 ACS patients (from November 2019 and May 2021), 79 who underwent PCI via a left radial approach (LRA) were included. We measured the angle of the left subclavian artery in the coronal view on CT imaging as an indicator of the tortuosity and investigated the association between that angle and the clinical variables and procedural time., Results: Patients with a left subclavian artery angle of a median of <70 degrees (severe tortuosity) were older (75.4 ± 11.7 vs. 62.9 ± 12.3 years, P < 0.001) and had a higher prevalence of female sex (42.1% vs. 14.6%, P =0.007), hypertension (94.7% vs. 75.6%, P =0.02), and subclavian artery calcification (73.7% vs. 34.2%, P < 0.001) than those with that ≥70 degrees. The left subclavian artery angle correlated negatively with the sheath cannulation to the first balloon time ( ρ  = -0.51, P < 0.001) and total procedural time ( ρ  = -0.32, P =0.004). A multiple linear regression analysis revealed that the natural log transformation of the sheath insertion to first balloon time was associated with a subclavian artery angle of <70 degrees ( β  = 0.45, P < 0.001)., Conclusion: Our study showed that lower left subclavian artery angles as a marker of the tortuosity via the LRA were strongly associated with a longer sheath insertion to balloon time and subsequent entire procedure time during the PCI., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Masatsugu Miyagawa et al.)

The patient is a 76-year-old man who underwent aortic and mitral valve replacement 30 years ago, both with mechanical valves. He had been on anticoagulant therapy with warfarin, which was switched to dabigatran two years ago by his primary care physician. He developed shortness of breath afterward and was taken to the hospital with heart failure. Fluoroscopy of the valve revealed that one leaflet of the prosthetic mitral valve was immobile. The patient was diagnosed with a thrombosed valve and underwent an urgency repeat mitral valve replacement. He recovered uneventfully and was discharged without complication. During long years, some patients may have comorbidities and get frail. Medical principle may change, and various treatment methods with more and more complex indications may emerge. But in patients with mechanical heart valves, warfarin still remains the only choice for anticoagulation therapy.

Stabilization of aortic vulnerable plaques has not been fully elucidated. Non-obstructive general angioscopy (NOGA) is a novel method for the detailed evaluation of atheromatous plaques in the aortic intimal wall. A 57-year-old man presenting with acute myocardial infarction underwent percutaneous coronary intervention (PCI). NOGA was performed for the evaluation of aortic atherosclerosis, and vulnerable puff-chandelier plaques in the aortic arch were identified. After a strictly controlled low-density lipoprotein cholesterol lowering therapy with a strong statin for 8 months after the primary PCI, NOGA revealed stabilized aortic plaques in the same lesions. Therefore, NOGA may be helpful in evaluating the effects of lipid-lowering therapy on aortic plaque stabilization.

Background: The possibility of permanent cardiovascular damage causing cardiovascular long COVID has been suggested; however, data are insufficient. This study investigated the prevalence of cardiovascular disorders, particularly in patients with cardiovascular long COVID using multi-modality imaging., Methods: A total of 584 patients admitted to the hospital due to COVID-19 between January 2020 and September 2021 were initially considered. Upon outpatient follow-up, 52 (9%) were suspected to have cardiovascular long COVID, had complaints of chest pain, dyspnea, or palpitations, and were finally enrolled in this study. This study is registered with the Japanese University Hospital Medical Information Network (UMIN 000047978)., Results: Of 52 patients with long COVID who were followed up in the outpatient clinic for cardiovascular symptoms, cardiovascular disorders were present in 27% (14/52). Among them, 15% (8/52) had myocardial injury, 8% (4/52) pulmonary embolisms, and 4% (2/52) both. The incidence of a severe condition (36% [5/14] vs. 8% [3/38], p = 0.014) and in-hospital cardiac events (71% [10/14] vs. 24% [9/38], p = 0.002) was significantly higher in patients with cardiovascular disorders than in those without. A multivariate logistic regression analysis revealed that a severe condition (OR, 5.789; 95% CI 1.442-45.220; p = 0.017) and in-hospital cardiac events (OR, 8.079; 95% CI 1.306-25.657; p = 0.021) were independent risk factors of cardiovascular disorders in cardiovascular long COVID patients., Conclusions: Suspicion of cardiovascular involvement in patients with cardiovascular long COVID in this study was approximately 30%. A severe condition during hospitalization and in-hospital cardiac events were risk factors of a cardiovascular sequalae in CV long COVID patients., 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., (Copyright © 2022 Murata, Yamada, Fujito, Hashimoto, Nagao, Tanaka, Fukumoto, Arai, Wakamatsu, Ebuchi, Monden, Kojima, Hayashi, Gon and Okumura.)

A battery-driven micro electromechanical system (MEMS) gas sensor has been developed for household safety when using natural gas. The heart of the MEMS gas sensor is a 7.5 at % Pt-SnO 2 thin film catalyst deposited on the SnO 2 sensor layer. The catalyst enhances the sensitivity to methane, though its structure under working conditions is unclear. In this study, in situ XAFS was applied to a 7.5 at % Pt-SnO 2 catalyst layer deposited on a Si substrate, and we demonstrated that atomically dispersed Pt maintains its lattice position in SnO 2 with a small loss of surrounding lattice oxygen in the presence of 1% CH 4 and a more reducing gas of 1% H 2 at the reaction temperature (703 K), i.e. , no Pt aggregation is observed. The lost oxygen is easily recovered by re-oxidation by air. This work has revealed that the atomically dispersed Pt in the SnO 2 lattice is the active structure and it is stable even under reaction conditions, which guarantees a long lifetime for the gas sensor.

Infection with cagA-positive Helicobacter pylori strains plays an etiological role in the development of gastric cancer. The CagA protein is injected into gastric epithelial cells through a bacterial Type IV secretion system. Inside the host cells, CagA promiscuously associates with multiple host cell proteins including the prooncogenic phosphatase SHP2 that is required for full activation of the Ras-ERK pathway. CagA-SHP2 interaction aberrantly activates SHP2 and thereby deregulates Ras-ERK signaling. Cancer is regarded as a disease of the genome, indicating that H. pylori-mediated gastric carcinogenesis is also associated with genomic alterations in the host cell. Indeed, accumulating evidence has indicated that H. pylori infection provokes DNA double-stranded breaks (DSBs) by both CagA-dependent and CagA-independent mechanisms. DSBs are repaired by either error-free homologous recombination (HR) or error-prone non-homologous end joining (NHEJ) or microhomology-mediated end joining (MMEJ). Infection with cagA-positive H. pylori inhibits RAD51 expression while dampening cytoplasmic-to-nuclear translocalization of BRCA1, causing replication fork instability and HR defects (known as "BRCAness"), which collectively provoke genomic hypermutation via non-HR-mediated DSB repair. H. pylori also subverts multiple DNA damage responses including DNA repair systems. Infection with H. pylori additionally inhibits the function of the p53 tumor suppressor, thereby dampening DNA damage-induced apoptosis, while promoting proliferation of CagA-delivered cells. Therefore, H. pylori cagA-positive strains promote abnormal expansion of cells with BRCAness, which dramatically increases the chance of generating driver gene mutations in the host cells. Once such driver mutations are acquired, H. pylori CagA is no longer required for subsequent gastric carcinogenesis (Hit-and-Run carcinogenesis)., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A large number of neurons form cell assemblies that process information in the brain. Recent developments in measurement technology, one of which is calcium imaging, have made it possible to study cell assemblies. In this study, we aim to extract cell assemblies from calcium imaging data. We propose a clustering approach based on non-negative matrix factorization (NMF). The proposed approach first obtains a similarity matrix between neurons by NMF and then performs spectral clustering on it. The application of NMF entails the problem of model selection. The number of bases in NMF affects the result considerably, and a suitable selection method is yet to be established. We attempt to resolve this problem by model averaging with a newly defined estimator based on NMF. Experiments on simulated data suggest that the proposed approach is superior to conventional correlation-based clustering methods over a wide range of sampling rates. We also analyzed calcium imaging data of sleeping/waking mice and the results suggest that the size of the cell assembly depends on the degree and spatial extent of slow wave generation in the cerebral cortex., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The clinical efficacy of the Impella for high-risk percutaneous coronary intervention (PCI) and cardiogenic shock remains under debate. We thus sought to investigate the protective effects on the heart with the Impella's early use pre-PCI using cardiac magnetic resonance imaging (CMRI)., Methods: We retrospectively evaluated the difference in the subacute phase CMR imaging results (19 ± 9 days after admission) between patients undergoing an Impella (n = 7) or not (non-Impella group: n = 18 [12 intra-aortic balloon pumps (1 plus veno-arterial extracorporeal membrane oxygenation) and 6 no mechanical circulation systems]) in broad anterior ST-elevation myocardial infarction (STEMI) cases. A mechanical circulation system was implanted pre-PCI., Results: No differences were found in the door-to-balloon time, peak creatine kinase, and hospital admission days between the Impella and non-Impella groups; however, the CMRI-derived left ventricular ejection fraction was significantly greater (45 ± 13% vs. 34 ± 7.6%, P = 0.034) and end-diastolic and systolic volumes smaller in the Impella group (149 ± 29 vs. 187 ± 41 mL, P = 0.006: 80 ± 29 vs. 121 ± 40 mL, P = 0.012). Although the global longitudinal peak strain did not differ, the global radial (GRS) and circumferential peak strain (GCS) were significantly higher in the IMPELLA than non-IMPELLA group. Greater systolic and diastolic strain rates (SRs) in the Impella than non-Impella group were observed in non-infarcted rather than infarcted areas., Conclusions: Early implantation of an Impella before PCIs for STEMIs sub-acutely prevented cardiac dysfunction through preserving the GRS, GCS, and systolic and diastolic SRs in the remote myocardium. This study provided mechanistic insight into understanding the usefulness of the Impella to prevent future heart failure., (© 2022. The Author(s).)

Aim: Coronary plaque rupture is the main cause of acute coronary syndrome (ACS), but the role of blood flow features around plaque rupture for ACS is still unknown. The present study aimed to assess the relationship between the geometric configuration of ruptured plaque and ACS occurrence using computational fluid dynamics (CFD) by moving particle method in patients with coronary artery disease., Methods: In this study, 45 patients with coronary artery disease who underwent three-dimensional intravascular ultrasound (IVUS) and had a coronary ruptured plaque (24 plaques with provoked ACS, 21 without) were included. To compare the difference in blood flow profile around ruptured plaque between the patients with and without ACS, the IVUS images were analyzed via the novel CFD analysis., Results: There were no significant differences in localized flow profile around ruptured plaque between the two groups when the initial particle velocity was 10.0 cm/s corresponded to a higher coronary flow velocity at ventricular diastole. However, when it was 1.0 cm/s corresponded to lower coronary flow velocity at ventricular systole, particles with lower velocity (0 ≤ V ≤ 5 cm/s) were more prevalent around ACS-PR ( p=0.035), whereas particles with higher velocity (10 ≤ V ≤ 20 cm/s) were more often detected in silent plaque ruptures (p=0.018)., Conclusions: Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.

Aims: Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation., Methods: In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n=53) and LDL-C/Apo B ＞1.2 group (high LDL-C/Apo B group, n=47)., Results: The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm 3 , p=0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) (p=0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) (p=0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p=0.017) than the high LDL-C/Apo B group., Conclusions: A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 μg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson's disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding., Competing Interests: No potential conflict of interest relevant to this article was reported.

Both cardiogenic shock (CS) and critical culprit lesion locations (CCLLs), defined as the left main trunk and proximal left anterior descending coronary artery, are associated with worse outcomes in ST-elevation myocardial infarctions (STEMIs). We aimed to examine how the combination of CS and/or CCLLs affected the prognosis in Japanese STEMI patients in the primary percutaneous coronary intervention era (PPCI-era). The subjects included 624 STEMI patients admitted to our hospital between January 2013 and April 2020. They were divided into four groups according to the combination of CS and CCLLs: CS (-) CCLL (-) group [n = 405], CS (-) CCLL (+) group [n = 150], CS (+) CCLL (-) group [n = 25], and CS (+) CCLL (+) group [n = 44]. The cumulative incidences of all-cause death at 30 days and 1 year were 3.5% and 6.4% in the CS (-) CCLL (-), 3.3% and 5.6% in the CS (-) CCLL (+), 32.0% and 32.0% in the CS (+) CCLL (-), and 50.0% and 65.9% in the CS (+) CCLL (+) group, respectively. After a multivariate adjustment, the CS (+) CCLL (+) group was independently associated with all-cause death (hazard ratio: 17.00, 95% confidence interval: 7.12-40.59 versus the CS (-) CCLL (-) group). In the CS (+) CCLL (+) group, compared to years 2013-2017, the IMPELLA begun to be used (44.4% versus 0%), and intra-aortic balloon pumps significantly decreased (44.4% versus 92.3%) during years 2018-2020, while the medications upon discharge did not significantly differ. The 30-day mortality was numerically lower during years 2018-2020 than years 2013-2017 (Log-rank test, P = 0.092). In conclusion, the prognosis of STEMIs varies greatly depending on the combination of CS and CCLLs, and in particular, patients with both CS and CCLLs had the poorest prognosis during the modern PPCI-era.

Background: Arbekacin (ABK) is an aminoglycoside that exhibits anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti- Pseudomonas aeruginosa activities. Therefore, for patients with febrile neutropenia (FN) and concurrent pneumonia suspected to be caused by MRSA, ABK may be sufficiently effective even as a single agent., Materials and Methods: Patients with hematologic malignancies treated with ABK who met the following criteria were included: 1) fever during neutropenia or functional neutropenia, 2) FN complicated by pneumonia, and 3) possible infection by antimicrobial-resistant Gram-positive cocci., Results: This study encompassed 22 episodes involving 19 patients, of which, 15 (68.2%) were successfully treated with ABK. Of the nine episodes showing inadequate response to other anti-MRSA drugs, eight were successfully treated with ABK. Grade 2 or worse adverse events included acute kidney injury (13.6%) and increased transaminase levels (9.1%)., Conclusion: The present study demonstrated that ABK is effective and safe in patients with FN and concurrent pneumonia caused by antimicrobial-resistant Gram-positive cocci. ABK may also be effective in patients who are unresponsive to other anti-MRSA drugs. Therefore, ABK may be beneficial in the treatment of pneumonia caused by antimicrobial-resistant Gram-positive cocci in patients with FN., Competing Interests: No conflict of interest., (Copyright © 2022 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Spatial active noise control (ANC) systems focus on minimizing unwanted acoustic noise over continuous spatial regions by generating anti-noise fields with secondary loudspeakers. Conventionally, error microphones are necessary inside the region to measure the channels from the secondary loudspeakers to the error microphones and record the residual sound field during the noise control. These error microphones highly limit the implementation of spatial ANC systems because of their impractical geometry and obstruction to the users from accessing the region. Recent advances, such as virtual sensing, focus on ANC with microphones placed away from the region. While these techniques relax the usage of error microphones during the noise control, an error microphone array remains necessary during the secondary channel estimation. In this paper, we propose a method to estimate secondary channels without using an error microphone array. Instead, a moving higher order microphone is applied to obtain the secondary channels from the secondary loudspeakers to the region of interest, which includes all desired error microphone locations. By simulation, we show that the proposed method is robust against various measuring errors introduced by the movement of the microphone and is suitable for the secondary channel estimation in spatial ANC systems.