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Abstract Background Chronic lymphocytic leukemia (CLL) is the rarest adult leukemia in Japan, whereas it is the most common leukemia in the Western world. Recent studies from the United States and Germany suggest a possible etiological association between Merkel cell polyomavirus (MCPyV) and CLL, although no data have been reported from Eastern countries. To increase the volume of relevant data, this study investigated the prevalence and DNA loads of MCPyV and human polyomavirus 9 (HPyV9), another lymphotropic polyomavirus, in Japanese CLL cases. Findings We found that 9/27 CLL cases (33.3 %) were positive for MCPyV using quantitative real-time polymerase chain reaction analysis. The viral DNA loads ranged from 0.000017 to 0.0012 copies per cell. All cases were negative for HPyV9. One MCPyV-positive CLL case was evaluated by mutational analysis of the large T (LT) gene, which indicated the presence of wild-type MCPyV without a nucleotide deletion. DNA sequence analysis of the entire small T (ST) gene and the partial LT gene revealed that a Japanese MCPyV isolate, designated CLL-JK, had two nucleotide gaps when compared with the reference sequence of the North American isolate MCC350. Conclusions This study provides the first evidence that MCPyV is present in a subset of Japanese CLL cases with low viral DNA loads. MCPyV and HPyV9 are unlikely to contribute directly to the development of CLL in the majority of Japanese cases. MCPyV isolated from the Japanese CLL cases may constitute an Asian group and its pathogenicity needs to be clarified in future studies.

Hypertension (HTN) is one of the major risk factors for developing atrial fibrillation (AF), and it has been estimated that approximately 70% of hypertensive patients are at risk of developing AF. On the other hand, 60-80% of AF patients have HTN. These two diseases share many risk factors such as diabetes mellitus, obesity, alcohol consumption, and sleep apnea syndrome during their onset and disease progression. The mutual presence of these diseases has the potential to create a negative spiral, exacerbating each other's impact and ultimately leading to cardiovascular events such as heart failure and cerebrovascular disorders, thereby increasing mortality rates. With regard to the treatment of HTN, the variety of antihypertensive drugs and treatment options have significantly increased. Alongside the widespread adoption of antihypertensive therapy, a certain level of efficacy has been recognized in suppressing the incidence of new-onset AF. Catheter ablation is an established and effective treatment for AF. However, a notable recurrence rate persists. In recent years, management of these multiple risk factors has been recognized to be essential for suppressing AF recurrence, and recent guidelines for AF underscore the significance of proactively managing these risks before treatment. Notably, effective HTN management assumes paramount importance given its impact on the morbidity of AF patients. This review summarizes the correlation between HTN control before and after ablation and the risk of AF recurrence. The focus is on elucidating the pathophysiological background and its impact on clinical outcomes., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Introduction: Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the differentiation have not been established. The present study aimed to develop new mixing test indexes for the differentiation., Methods: Twenty-six LA-positive, 8 progressive coagulation factor VIII inhibitor, and 35 coagulation deficient samples were employed. APTT were measured for normal plasma, patient plasma, and mixing plasma prepared at a ratio of 1:1 proportion in both without incubation and 2 h-incubation. New two parameters named as ALD50 and mixture plasma-patient plasma after Warming change rate Subtraction (WaS) calculated from the clotting times of normal, 1:1 mixing and patient samples with/without 2 h-incubation were established. In the samples with WaS result of <10.2%, ALD50 of ≥87.8%, and < 87.8% were defined as LA and coagulation factor deficiency, respectively, and WaS of ≥10.2% defined progressive coagulation factor inhibitors., Results: Sensitivity and specificity to LA were 80.8% and 93.0% for ALD50, and sensitivity and specificity to progressive coagulation factor inhibitor were 100.0% and 100.0% for WaS, respectively. The agreement between sample classification and WaS-ALD50 was 88.4% (61/69)., Conclusions: ALD50 and WaS showed acceptable sensitivity and specificity to LA and progressive coagulation factor inhibitor, respectively. These indexes would be useful for the differentiation between LA, factor deficiency, and progressive coagulation factor inhibitor in the mixing tests., (© 2024 John Wiley & Sons Ltd.)

Olfactory dysfunction is associated with aging and the earliest stages of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases; it is thought to be an early biomarker of cognitive decline. In marmosets, a small non-human primate model used in brain research, olfactory pathway activity during olfactory stimulation has not been well studied because of the difficulty in clearly switching olfactory stimuli inside a narrow MRI. Here, we developed an olfactory-stimulated fMRI system using a small-aperture MRI machine. The olfactory presentation system consisted of two tubes, one for supply and one for suction of olfactory stimulants and a balloon valve. A balloon valve installed in the air supply tube controlled the presentation of the olfactory stimulant, which enabled sharp olfactory stimulation within MRI, such as 30 s of stimulation repeated five times at five-minute intervals. The olfactory stimulation system was validated in vivo and in a simulated system. fMRI analysis showed a rapid increase in signal values within 30 s of olfactory stimulation in eight regions related to the sense of smell. As these regions include those associated with Alzheimer's and Parkinson's diseases, olfactory stimulation fMRI may be useful in clarifying the relationship between olfactory dysfunction and dementia in non-human primates., (© 2024. The Author(s).)

Mycoplasma bovis mastitisis highly contagious and disrupts lactation, posing a significant threat to the dairy industry. While the mammary gland's defence mechanism involves epithelial cells and mononuclear cells (MNC), their interaction with M. bovis remains incompletely understood. In this study, we assessed the immunological reactivity of bovine mammary epithelial cells (bMEC) to M. bovis through co-culture with MNC. Upon co-culture with MNC, the mRNA expression levels of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α in bMEC stimulated by M. bovis showed a significant increase compared to monoculture. Additionally, when stimulated with M. bovis, the culture supernatant exhibited significantly higher concentrations of IL-6 and interferon (IFN)-γ, while IL-1β concentration tended to be higher in co-culture with MNC than in monoculture. Furthermore, the mRNA expression levels of toll-like receptor (TLR) 2 in bMEC stimulated with M. bovis tended to increase, and TLR4 significantly increased when co-cultured with MNC compared to monocultures. However, the surface expression levels in bMEC did not exhibit significant changes between co-culture and monoculture. Overall, our research indicates that the inflammatory response of bMEC is increased during co-culture with MNC, suggesting that the interaction between bMEC and MNC in the mammary gland amplifies the immune response to M. bovis in cows affected by M. bovis mastitis.

Lack of the typical nocturnal blood pressure (BP) fall, i.e non-dipper, has been known as a cardiovascular risk. However, the influence of non-dipper on atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been unclear. We investigated the clinical impact of non-dipping as evaluated by 24-hour ambulatory BP monitoring on the long-term outcome of AF recurrence post-PVI in 76 AF patients with a history of increased BP. The PVI procedure was successful in all 76 patients (mean age, 66±9years; antihypertensive medication, 89%; non-paroxysmal AF, 24%). Twenty patients had AF recurrence during a median follow-up of 1138 days. There was no difference in BP levels between the AF recurrence and non-recurrence groups (average 24 h systolic BP:126 ± 17 vs.125 ± 14 mmHg; P = 0.84). On the other hand, the patients with non-dipper had a higher AF recurrence than those with dipper (38.9% vs.15.0%; P = 0.018). In Cox hazard analysis adjusted by age, non-paroxysmal AF and average 24-hr systolic BP level, the non-dipper was an independent predictor of AF recurrence (HR 2.78 [95%CI:1.05-7.34], P = 0.039). Non-dipper patients had a larger left atrial (LA) volume index than the dipper patients (45.9 ± 17.3 vs.38.3 ± 10.2 ml/m 2 , P = 0.037). Among the 58 patients who underwent high-density voltage mapping in LA, 11 patients had a low-voltage area (LVA) defined as an area with a bipolar voltage < 0.5 mV. However, there was no association of LVA with non-dipper or dipper (22.2% vs.16.1%, P = 0.555). Non-dipper is an independent predictor of AF recurrence post-PVI. Management of abnormal diurnal BP variation post-PVI may be important., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Pulmonary vein stenosis (PVS) is a serious complication of catheter ablation (CA) for atrial fibrillation (AF). PVS generally occurs several months after CA and presents with non-specific symptoms and imaging findings. There have been reports of delayed diagnoses due to a misdiagnosis as infection, interstitial pneumonia, or organizing pneumonia. We introduced six cases of PVS after CA, all of which showed narrowing of the unilateral pulmonary vessels with or without lobar volume loss in the left lung on unenhanced computed tomography. We report these findings as important results indicating the possibility of PVS after CA for AF and contributing to the early diagnosis and management of PVS.

Background: Laboratory testing of large sample numbers necessitates high-volume rapid processing, and these test results require immediate validation and a high level of quality assurance. Therefore, real-time quality control including delta checking is an important issue. Delta checking is a process of identifying errors in individual patient results by reviewing differences from previous results of the same patient (Δ value). Under stable analytical conditions, Δ values are equally positively and negatively distributed., Methods: The previous 20 Δ values from 3 tests (cholesterol, albumin, and urea nitrogen) were analyzed by calculating the R-value: "the positive Δ value ratio minus 0.5." This method of monitoring optimized R-values is referred to as the even-check method (ECM) and was compared with quality control (QC) testing in terms of error detection., Results: Bias was observed on 4 of the 120 days for the 3 analytes measured. When QC detected errors, the ECM captured the same systematic errors and more rapidly. In contrast, the ECM did not generate an alarm for the one random error that occurred in QC. While QC did not detect any errors, the percentage of R-values exceeding the acceptable range was under 2%, the number of days generating alarms was between 16 and 21 days, with short alarm periods, and a median number of samples per alarm period between 7 and 9 samples., Conclusions: The ECM is a practical real-time QC method, controlled by setting R-value conditions, that quickly detects bias values., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Assessment of social interactions and behavioral changes in nonhuman primates is useful for understanding brain function changes during life events and pathogenesis of neurological diseases. The common marmoset (Callithrix jacchus), which lives in a nuclear family like humans, is a useful model, but longitudinal automated behavioral observation of multiple animals has not been achieved. Here, we developed a Full Monitoring and Animal Identification (FulMAI) system for longitudinal detection of three-dimensional (3D) trajectories of each individual in multiple marmosets under free-moving conditions by combining video tracking, Light Detection and Ranging, and deep learning. Using this system, identification of each animal was more than 97% accurate. Location preferences and inter-individual distance could be calculated, and deep learning could detect grooming behavior. The FulMAI system allows us to analyze the natural behavior of individuals in a family over their lifetime and understand how behavior changes due to life events together with other data., (© 2024. The Author(s).)

Background: The precise details of atrial activation around the triangle of Koch (ToK) remain unknown. We evaluated the relationship between the atrial-activation pattern around the ToK and success sites for slow-pathway (SP) modification ablation in slow-fast atrioventricular reentrant tachycardia (AVNRT)., Methods: Thirty patients with slow-fast AVNRT who underwent successful ablation were enrolled. Atrial activation around the ToK during sinus rhythm was investigated using ultra-high-density mapping pre-ablation. The relationships among features of atrial-activation pattern and success sites were examined., Results: Of 30 patients (22 cryoablation; 8 radiofrequency ablation), 26 patients had a collision site of two wavefronts of delayed atrial activation within ToK, indicating a success site. The activation-search function of Lumipoint software, which highlights only atrial activation with a spatiotemporal consistency, showed non-highlighted area on the tricuspid-annulus side of ToK. In 23 of the patients, a spiky potential was recorded at that collision site outside the Lumipoint-highlighted area. Fifteen cryoablation patients with a success site coincident with a collision site outside the Lumipoint-highlighted area had significantly more frequent disappearances of SP after initial cryoablation (46.7% vs. 0%, p  = .029), fewer cryoablations (3.7 ± 1.8 vs. 5.3 ± 1.3, p  = .045), and shorter procedure times (170 ± 57 vs. 228 ± 91 min, p  = .082) compared to the seven cryoablation patients without such sites. Four patients had transient AV block by ablation inside the Lumipoint-highlighted area with fractionated signals, but no patient developed permanent AV block or recurrence post-procedure (median follow-up: 375 days)., Conclusions: SP modification ablation at the collision site of atrial activation of the tricuspid-annulus side along with a spiky potential could provide a better outcome., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Hemoglobin variants are often discovered when hemoglobin A1c (HbA1c) levels measured with a high-performance liquid chromatography (HPLC) system in fast mode are found to be low. The HA-8180V HPLC analyzer by Arkray offers two measurement modes: fast mode (FM) and variant mode (VM). Two Japanese patients with α-chain variant Hb Q-Iran detected incidentally after analyses with the HA-8180V in VM showed an abnormal peak, are presented. The first patient was a man in his 70 s, and the second patient was a man in his 50 s. Both were non-diabetic, but their results from HbA1c measurement in VM showed an abnormal peak. The VM-HbA1c, FM-HbA1c, and HbA1c measured by enzymatic assay and glycated albumin levels of the two patients were all within the reference ranges. They were diagnosed as having Hb Q-Iran (α2-75Asp → His) by globin gene analysis. It is difficult to detect α-chain hemoglobin variants based on abnormal FM-HbA1c levels, but measuring HbA1c in VM is useful for efficiently detecting hemoglobin variants., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Japan Diabetes Society 2024.)

Aims: The relationship between local unipolar voltage (UV) in the pulmonary vein (PV)-ostia and left atrial wall thickness (LAWT) and the utility of these parameters as indices of outcome after atrial fibrillation (AF) ablation remain unclear., Methods and Results: Two-hundred seventy-two AF patients who underwent AF ablation were enrolled. Unipolar voltage of PV-ostia was measured using a CARTO system, and LAWT was measured using computed tomography. The primary endpoint was atrial tachyarrhythmia (ATA) recurrence including AF. The ATA recurrence was documented in 74 patients (ATA-Rec group). The UV and LAWT of the bilateral superior PV roof to posterior and around the right-inferior PV in the ATA-Rec group were significantly greater than in patients without ATA recurrence (ATA-Free group) (P < 0.001). The UV had a strong positive correlation with LAWT (R2 = 0.446, P < 0.001). The UV 2.7 mV and the corresponding LAWT 1.6 mm were determined as the cut-off values for ATA recurrence (P < 0.001, respectively). Multisite LA high UV (HUV, ≥4 areas of >2.7 mV) or multisite LA wall thickening (≥5 areas of >1.6 mm), defined as LA hypertrophy (LAH), was related to higher ATA recurrence. Among 92 LAH patients, 66 had HUV (LAH-HUV) and the remaining 26 had low UV (LAH-LUV), characterized by history of non-paroxysmal AF and heart failure, reduced LV ejection fraction, or enlarged LA. In addition, LAH-LUV showed the worst ablation outcome, followed by LAH-HUV and No LAH (log-rank P < 0.001)., Conclusion: Combining UV and LAWT enables us to stratify recurrence risk and suggest a tailored ablation strategy according to LA tissue properties., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: While most VVI pacemakers in bradycardic patients are set to a low limit of 60/min, the optimal lower limit rate for VVI pacemakers in atrial fibrillation has not been established. Although an increase in heart rate within the normal range in the setting of a VVI pacemaker might be expected to lead to an increase in cardiac output with the shortening of the diastolic time, the changes in cardiac output at different pacemaker settings have not been fully clarified., Methods: We included 11 patients with bradycardic atrial fibrillation who had VVI pacemakers implanted. Stroke volume was measured using the electrical cardiometry method (AESCULON Ⓡ mini; Osypka Medical) without pacing and at ventricular pacings of 60, 70, 80, and 90/min., Results: Stroke volume decreased stepwise at ventricular pacing rates of 60, 70, 80, and 90/min (63.6 ± 11.2, 61.9 ± 10.6, 59.3 ± 12.2, and 57.5 ± 12.2 mL, p  < .001), but cardiac output increased (3.81 ± 0.67, 4.33 ± 0.74, 4.74 ± 0.97, and 5.17 ± 1.09 L/min, p  < .001). The rate of increase in cardiac output at a pacing rate of 70/min compared to 60/min correlated with left ventricular end-systolic volume ( r  = 0.711, p  = .014)., Conclusions: Cardiac output increased at a pacing rate of 70 compared to 60 in bradycardic atrial fibrillation patients, and the rate of increase in cardiac output was greater in those with larger left ventricular end-systolic volume., Competing Interests: There are no conflicts of interest in the context of this study. TK reports research and education support from Medtronic, Japan Lifeline, and Abbott. KK reports honoraria from Medtronic outside the submitted work., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Introduction: Beyond pulmonary vein isolation (PVI), additional therapeutic strategies for atrial fibrillation (AF) have not been established. Remodeling of the left atrium (LA) could impact AF recurrence post-PVI. We investigated the impact of unipolar voltage (UV) criteria for the LA posterior wall (LA-PW) on AF recurrence post-PVI., Methods: We reviewed the cases of 106 AF patients (mean age 63.8 years, nonparoxysmal AF: 59%) who underwent extensive encircling PVI by radiofrequency ablation guided by a 3-dimension mapping system, investigating the impact on AF recurrence of the UV criteria of the LA., Results: Out of all patients, 26 patients had AF recurrence during post-PVI follow-up [median 603 days]. They showed a higher percentage of nonparoxysmal AF (80.8 vs. 52.5%, p = .011), longer AF duration (2.9 ± 2.7 vs. 1.0 ± 1.7 years, p = .002), and larger area size of UV < 2.0 mV in LA-PW (2.8 ± 1.8 vs. 1.0 ± 1.5 cm 2 , p < .001) than those without recurrence. Cox Hazard analysis for AF recurrence adjusted by age, gender, AF duration, body mass index and left atrial volume index revealed that an area size over 2.0 cm 2 of UV < 2.0 mV in LA-PW (HR 6.9 [95% CI:1.3-35.5], p = .021) posed independent risks for AF recurrence post-PVI. The atrial arrhythmia-free survival rate was higher in those with no area of UV < 3.0 mV in LA-PW compared to those with a sizable area (>2.0 cm 2 ) of UV < 3.0 mV and <2.0 mV (95.0% vs. 74.2% vs. 57.1%, Log-Rank: p < .001). In the AF etiology of patients with AF recurrence, 9 of 14 patients who underwent the 2nd procedure had no PV reconnection, and 8 patients required the LA-PW isolation for their non-PV AF., Conclusion: UV criteria of LA-PW is a useful parameter for AF-recurrence post-PVI. Lower UV in LA-PW as an indication of electrical remodeling could indicate a higher risk of AF recurrence and the need for further therapeutic strategies., (© 2023 Wiley Periodicals LLC.)

Aims: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). The most frequent complication during CB-based PVI is right-sided phrenic nerve injury (PNI) which is leading to premature abortion of the freeze cycle. Here, we analysed reconnection rates after CB-based PVI and PNI in a large-scale population during repeat procedures., Methods and Results: In the YETI registry, a total of 17 356 patients underwent CB-based PVI in 33 centres, and 731 (4.2%) patients experienced PNI. A total of 111/731 (15.2%) patients received a repeat procedure for treatment of recurrent AF. In 94/111 (84.7%) patients data on repeat procedures were available. A total of 89/94 (94.7%) index pulmonary veins (PVs) have been isolated during the initial PVI. During repeat procedures, 22 (24.7%) of initially isolated index PVs showed reconnection. The use of a double stop technique did non influence the PV reconnection rate (P = 0.464). The time to PNI was 140.5 ± 45.1 s in patients with persistent PVI and 133.5 ± 53.8 s in patients with reconnection (P = 0.559). No differences were noted between the two populations in terms of CB temperature at the time of PNI (P = 0.362). The only parameter associated with isolation durability was CB temperature after 30 s of freezing. The PV reconnection did not influence the time to AF recurrence., Conclusion: In patients with cryoballon application abortion due to PNI, a high rate of persistent PVI rate was found at repeat procedures. Our data may help to identify the optimal dosing protocol in CB-based PVI procedures., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03645577?term=YETI&cntry=DE&draw=2&rank=1 ClinicalTrials.gov Identifier: NCT03645577., Competing Interests: Conflict of interest: C.H.H. received travel grants and research grants from Medtronic, Boston Scientific, Biosense Webster and Cardiofocus and is a proctor and lecturer of Medtronic, Boston Scientific, Cardiofocus and Biosense Webster. K.H.K. received travel grants and research grants from Biosense Webster, Stereotaxis, Prorhythm, Medtronic, Edwards, Cryocath, and is a consultant to St. Jude Medical, Biosense Webster, Prorhythm, and Stereotaxis. He received speaker's honoraria from Medtronic. R.R.T. received travel grants from St. Jude Medical, Biosense Webster, Daiichi Sankyo, SentreHeart and Speaker’s Bureau Honoraria from Biosense Webster, Biotronik, Boston scientific, Pfizer, Topera, Bristol-Myers Squibb, Bayer, Sanofi Aventis, and research grants by Cardiofocus, Boston Scientific and Lifetech. K.A. is a proctor and lecturer for Medtronic, Biosense Webster, and Abbott. A.M. received speaker's honoraria and travel grants from Medtronic, Biosense Webster and Cardiofocus. F.S. received honoraria for lectures from Medtronic, Philips EPD Solutions, and Bristol-Myers-Squibb, outside the submitted work; and educational support from Pfizer. S.C. received travel grants and speaker’s honoraria from Medtronic, Biosense Webster and Abbott, and is a proctor of Medtronic. E.J.P. received consultant fees from Medtronic, Biotronik, Abbott, Boston Scientific. E.W. is a consultant to Medtronic. All other authors have no relevant disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Rapid positive blood culture reporting allows early and appropriate treatment of severe infections to improve patient prognosis. This study evaluated performance of the VersaTREK system with gas pressure detection and tornado stirring method and the conventional BacT/ALERT 3D system. Time to positivity (TTP) of simulated blood cultures without whole blood using 17 ATCC strains was faster with VersaTREK than BacT/ALERT 3D, averaging 6.3 h in aerobic bottles and 12.7 hours in anaerobic bottles. In simulated blood cultures with whole blood using 53 clinical isolates, on average, VersaTREK was faster in aerobic bottles by 6.5 h but slower in anaerobic bottles by 3.8 h. Fifty of 53 simulated blood cultures with whole blood (94%) showed fastest TTP with VersaTREK. TTP of VersaTREK for anaerobic bacteria Bacteroides fragilis and Clostridium perfringens , Helicobacter cinaedi , and Candida glabrata was fast, and viable bacteria numbers in bottles using the Miles and Misra method increased quickly.

Purpose: Cryoablation is a safe alternative to radiofrequency (RF) ablation for slow-fast atrioventricular reentrant tachycardia (AVNRT); however, optimal electrogram parameters for site selection remain unknown. We retrospectively investigated local electrograms for slow pathway (SP) modification in cryoablation., Methods: Forty-five consecutive patients with slow-fast AVNRT who underwent cryoablation using a 6-mm-tip catheter were enrolled. Electrogram parameters for sites of successful SP modification (success-sites) were investigated; these included the interval between atrial activation at His and the last deflection of SP potential, defined as the His(A)-SPP interval. In 8 patients, 3-dimensional mapping by multi-electrode catheter was performed pre-ablation for more detailed SP assessment., Results: Twenty-seven of 45 patients had successful SP modification by 1 cycle of freeze-thaw-freeze cryoablation at a single site with a low amplitude and fragmented SP potential. Among a total of 76 cryoablation sites in all patients, the His(A)-SPP interval at success-sites (45 sites) was significantly longer than that at unsuccess-sites (31 sites) (86 ± 9 vs.78 ± 10 msec, p < 0.0001). The AV amplitude ratio was not significantly different between success-and unsuccess-sites (0.21 ± 0.22 vs.0.25 ± 0.23, p = 0.429). The cutoff value of the His(A)-SPP interval for successful cryoablation was 82 msec with a sensitivity of 0.67 and specificity of 0.71 (AUC: 0.739; 95%CI: 0.626-0.852; p < 0.0001). Three-dimensional mapping in all 8 patients showed that sites with the most delayed atrial activation and the last deflection of the fragmented SP potential within the Koch's triangle coincided with success-sites., Conclusion: A longer His(A)-SPP interval and fractionated SP potential were characteristics of successful cryoablation for SP modification in slow-fast AVNRT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate the safety and efficacy of high-power short-duration (HP-SD) ablation compared to conventional ablation in patients with atrial fibrillation (AF)., Methods: We enrolled consecutive 158 drug-refractory symptomatic AF patients (119 males, mean age 63 ± 10 years) who had undergone first radiofrequency pulmonary vein isolation (PVI). PVI was performed using the conventional setting (20-35 W) in 73 patients (Conventional group) and using the HP-SD setting (45-50 W) in 85 patients (HP-SD group). The rate of first pass isolation, remaining gaps after circumferential ablation, dormant conduction, and the radiofrequency application time in each pulmonary vein (PV) were compared between the groups., Results: The first pass isolation ratio was significantly higher in the HP-SD group than in the Conventional group (81% vs. 65%, P = 0.027) in the right PV, but did not differ in the left PV. The remaining gaps were fewer in the right superior PV (4% vs. 21%, P = 0.001) and left inferior PV (1% vs. 8%, P = 0.032) areas, and the radiofrequency application time in each PV was shorter (right PV, 12.0 ± 8.9 min vs. 34.0 ± 31.7 min, P < 0.001; left PV, 10.6 ± 3.6 min vs. 25.7 ± 22.3 min, P < 0.001) in the HP-SD group than in the Conventional group., Conclusion: The use of the HP-SD setting might contribute to improve the first pass isolation rate and to shorten the radiofrequency application time in each PV., (© 2022. The Author(s).)

Paneth cells are intestinal epithelial cells that release antimicrobial peptides, such as α-defensin as part of host defense. Together with mesenchymal cells, Paneth cells provide niche factors for epithelial stem cell homeostasis. Here, we report two subtypes of murine Paneth cells, differentiated by their production and utilization of fucosyltransferase 2 (Fut2), which regulates α(1,2)fucosylation to create cohabitation niches for commensal bacteria and prevent invasion of the intestine by pathogenic bacteria. The majority of Fut2 - Paneth cells were localized in the duodenum, whereas the majority of Fut2 + Paneth cells were in the ileum. Fut2 + Paneth cells showed higher granularity and structural complexity than did Fut2 - Paneth cells, suggesting that Fut2 + Paneth cells are involved in host defense. Signaling by the commensal bacteria, together with interleukin 22 (IL-22), induced the development of Fut2 + Paneth cells. IL-22 was found to affect the α-defensin secretion system via modulation of Fut2 expression, and IL-17a was found to increase the production of α-defensin in the intestinal tract. Thus, these intestinal cytokines regulate the development and function of Fut2 + Paneth cells as part of gut defense., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

There are no studies examining interventricular (VV) delay optimization by an electrical cardiometry method in relation to subsequent cardiac function in cardiac resynchronization therapy (CRT) -implanted patients. This study aimed to compare the VV delay in CRT-implanted patients by the dp/dt and electrical cardiometry and to examine the optimization of VV delay and improvement of cardiac function. We examined 19 consecutive CRT-implanted patients. The protocol included biventricular stimulation with either simultaneous or sequential pacing, and we evaluated systolic volume (SV) using an electrical cardiometry and the dp/dt of the left ventricle. The optimal VV delay was determined by the maximum SV using the electrical cardiometry. Two groups were defined, those whose increase in SV was at or above the median and those whose SV increase was below the median; changes in left ventricular ejection fraction (LVEF). The correlation between the VV delay optimized by the electrical cardiometry and dp/dt methods was high (R = 0.61, P = 0.006). Compared to the baseline SV (43.4 mL), the SV increased to 47.8 mL with simultaneous biventricular pacing (versus baseline P = 0.008) and further increased to 49.8 mL with optimized VV delay (versus simultaneous biventricular pacing P = 0.020). LVEF after 6 months significantly improved in the above-median SV increase group (37.6 versus 28.2%, P = 0.041), but not in the below-median SV increase group (26.5 versus 26.5%, P = 0.985). In conclusion, the optimal VV delay by electrical cardiometry method was almost concordant with that by the dp/dt method. Cardiac function significantly improved in the group with the above-median SV increase.