Publications by authors named "Ryo Watanabe"

118 Publications

Depolarization and repolarization dynamics after His-bundle pacing: Comparison with right ventricular pacing and native ventricular conduction.

Ann Noninvasive Electrocardiol 2022 Jul 8:e12991. Epub 2022 Jul 8.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: The current study aimed to evaluate changes in electrical depolarization and repolarization parameters after His-bundle pacing (HBP) compared with right ventricular pacing (RVP) and its association with ventricular arrhythmia (VA).

Methods: Forty-one patients (13 with HBP, 14 with RVP, and 14 controls [AAI mode]) were evaluated. After continuous pacing algorithm, QRS duration, QT interval, QTc, JT interval, T-peak to T-end (Tpe), and Tpe/QT ratio were measured on electrocardiography at baseline and 1 week, 1 month, and 6 months postoperatively. We investigated VA occurrence and adverse events after implantation.

Results: At 6 months, QRS duration was significantly shorter in the HBP (121.6 ± 15.6 ms) than in the RVP (150.1 ± 14.9 ms) group. The QT intervals were lower in the HBP (424.0 ± 40.9 ms) and control (405.9 ± 23.0 ms) groups than in the RVP (453.0 ± 40.2 ms) group. The Tpe and Tpe/QT ratios at 6 months differed significantly between the HBP and RVP groups (Tpe, 69.8 ± 19.7 ms vs 87.4 ± 11.9 ms and Tpe/QT, 0.16 ± 0.03 vs 0.19 ± 0.02, respectively). The Tpe and Tpe/QT ratios were similarly shortened in the HBP and control groups. VA occurred less frequently in the HBP (15%) and control (7.1%) groups than in the RVP (50%) group (p = 0.020). The non-RVP group showed significantly lower rates of VA and major adverse events than the RVP group. Patients with VA demonstrated significantly longer QRS duration, QT interval, Tpe, and Tpe/QT at 6 months than those without VA.

Conclusion: HBP showed better depolarization and repolarization stability than RVP.
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http://dx.doi.org/10.1111/anec.12991DOI Listing
July 2022

Checking the validity and reliability of the Japanese version of the Mini-Cog using a smartphone application.

BMC Res Notes 2022 Jun 25;15(1):222. Epub 2022 Jun 25.

Graduate School of Health Innovation, Kanagawa University of Human Services, Research Gate Building TONOMACHI 2-A, 3-25-10 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-0821, Japan.

Objective: Cognitive decline is an important and well-documented health problem. The Mini-Cog, a simple cognitive function test, is recommended as a potential early cognitive screening tool. Kanagawa Prefecture, one of the largest prefectures in Japan, developed this self-testing application on a smartphone to enable a large number of residents to assess their cognitive function. This study aimed to verify the validity and reliability of the Mini-Cog.

Results: Twenty men and 20 women aged 65-85 years were enrolled. Criterion-related validity of the method tested by professional staff was found to have an acceptable positive association. The test-retest reliability was lower than the clinically expected intraclass correlation coefficient value because of the inclusion of learning and order effects. If the Mini-Cog score of this application is low, the system is equipped with a function that advises the users on preventing cognitive decline, directing them to the appropriate services, and recommending visits to a medical institution. Therefore, the system can be used continuously as a tool for health behaviors and promotions.
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http://dx.doi.org/10.1186/s13104-022-06101-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233764PMC
June 2022

Impact of synchronized left ventricular pacing rate on risk for ventricular tachyarrhythmias after cardiac resynchronization therapy in patients with heart failure.

J Interv Card Electrophysiol 2022 Jun 23. Epub 2022 Jun 23.

Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Background: The adaptive cardiac resynchronization therapy (aCRT) algorithm automatically produces synchronized left ventricular pacing (sLVP) with intrinsic atrioventricular conduction to improve clinical outcomes. However, relationship between sLVP percentage and risk for ventricular tachyarrhythmia (VT/VF) remains unclear. This study aimed to evaluate the clinical impact of sLVP rate on VT/VF occurrence.

Methods: In total, 1,419 device interrogation data from 42 consecutive patients who underwent new aCRT device implantation were retrospectively analyzed. The primary endpoint was the first time VT/VF episode after aCRT device implantation.

Results: During a median follow-up of 34 months, 15 patients had VT/VF episodes. Patients were divided into a high sLVP (the average sLVP percentage of ≥ 51.5%, n = 27) or low sLVP group (< 51.5%, n = 15). The high sLVP group had a significantly lower VT/VF incidence (22% vs. 60%; p = 0.014) and an independent predictor for VT/VF occurrence on multivariate analysis (hazard ratio 0.21; p = 0.007). LV ejection fraction improvements after 6 months (12.3 ± 8.7% vs. 2.8 ± 10.3%; p = 0.004) and 12 months (13.8 ± 9.3% vs. 6.2 ± 11.1%; p = 0.030) were significantly greater in the high sLVP group than in the low sLVP group. Age, PR interval, and left atrial diameter were significantly associated with the sLVP rate after aCRT.

Conclusions: Patients with high sLVP percentage after aCRT had lower long-term risk of VT/VF incidence with a favorable response to CRT. A synchronized pacing algorithm using intrinsic conduction may prevent malignant arrhythmias, as well as recover cardiac functions.
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http://dx.doi.org/10.1007/s10840-022-01284-zDOI Listing
June 2022

Coagulation Response and Prothrombotic Effect of Uninterrupted Oral Anticoagulant Administration After Catheter Ablation for VT.

JACC Clin Electrophysiol 2022 06 27;8(6):735-748. Epub 2022 Apr 27.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Catheter ablation for ventricular tachycardia (VT) is associated with perioperative thromboembolic risk. However, the strategy for postprocedural management remains unknown.

Objectives: The aim of this study was to evaluate the prothrombotic response after VT ablation in various coagulation biomarkers in patients with and without the administration of oral anticoagulation (OAC).

Methods: Data from 112 patients (58 with uninterrupted OAC and 54 without) with structural heart disease who underwent endocardial VT ablation were retrospectively analyzed. We also included 41 patients who underwent ablation for premature ventricular contraction from the right ventricle and 13 patients who underwent electrophysiology study (the control group). Blood samples of coagulation markers were collected before and 3 days after the procedure in all patients.

Results: The percentage of D-dimer levels ≤1.0 μg/mL at baseline was lower in the VT ablation groups (76% and 50% in the OAC and non-OAC groups, respectively) than in the other groups (100%). After 3 days, the percentage remained at 67% in the OAC group; however, the non-OAC VT group demonstrated a remarkable decrease of 20%. Similarly, fibrin monomer complex, thrombin antithrombin, and prothrombin fragment 1+2 levels were well suppressed in the control, premature ventricular contraction, and OAC groups. However, the non-OAC group demonstrated increased coagulation markers both before and after 3 days. Multivariate analysis demonstrated that OAC administration and normal coagulation markers at baseline were independent predictors of stable coagulation status after ablation.

Conclusions: The coagulation cascade was significantly activated in patients undergoing VT ablation. Uninterrupted OAC administration suppressed the coagulation response, which might be associated with a reduction in perioperative prothrombotic risk.
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http://dx.doi.org/10.1016/j.jacep.2022.02.015DOI Listing
June 2022

A selective hybrid fluorescent sensor for fructose detection based on a phenylboronic acid and BODIPY-based hydrophobicity probe.

RSC Adv 2022 May 18;12(24):15083-15090. Epub 2022 May 18.

Department of Bioscience and Biotechnology, Faculty of Bioscience and Biotechnology, Fukui Prefectural University 4-1-1 Matsuoka-Kenjojima, Eiheiji Fukui 910-1195 Japan

Fructose is widely used in the food industry. However, it may be involved in diseases by generating harmful advanced glycation end-products. We have designed and synthesized a novel fluorescent probe for fructose detection by combining a phenylboronic acid group with a BODIPY-based hydrophobicity probe. This probe showed a linear fluorescence response to d-fructose concentration in the range of 100-1000 μM, with a detection limit of 32 μM, which is advantageous for the simple and sensitive determination of fructose.
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http://dx.doi.org/10.1039/d2ra01569bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116957PMC
May 2022

Evaluation of the Novel Automated Anti-Tachycardia Pacing Algorithm Successfully Terminating Sustained Monomorphic Ventricular Tachycardia in an Electrophysiology Study.

Int Heart J 2022 ;63(3):633-638

Department of Cardiology, Nagoya University Graduate School of Medicine.

We report the usefulness of novel automated anti-tachycardia pacing (ATP) for ventricular tachycardia (VT) termination evaluated in an electrophysiology study. This intrinsic, automated ATP with an implanted cardiac resynchronization therapy-defibrillator successfully terminated the sustained VT, which had not been suppressed by repetitive burst pacing from the electrode catheter. The reproduction of programed pacing of the automated ATP by a right ventricular electrode catheter was effective in terminating VT, and this termination was absolute and reproducible. Further detailed assessment in an electrophysiology study could highlight the algorithm of the automated ATP and its possible benefit in terminating the reentrant VT.
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http://dx.doi.org/10.1536/ihj.21-755DOI Listing
June 2022

Characteristics of successful reactive atrial-based antitachycardia pacing in patients with cardiac implantable electronic devices: History of catheter ablation of atrial fibrillation as a predictor of high treatment efficacy.

J Cardiovasc Electrophysiol 2022 07 27;33(7):1515-1528. Epub 2022 May 27.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Introduction: Reactive atrial-based antitachycardia pacing (rATP) in patients with cardiac implantable electronic devices (CIEDs) suppresses the progression of atrial fibrillation (AF) to the persistent form. However, the clinical factors associated with successful reactive atrial-based antitachycardia pacing (rATP) treatment are unknown. This study aimed to examine the predictors of high rATP efficacy in patients with CIEDs.

Methods: The data of 101,325 rATP-treated atrial tachyarrhythmia (AT/AF) episodes in 51 patients, obtained through remote monitoring and device interrogation, were analyzed. The study population was divided into the high and low efficacy groups based on the overall median success rate of rATP. Clinical characteristics were compared between the two groups.

Results: During a follow-up period of 28.6 ± 8.6 months, the median success rate was 43.7% (31.5%-64.9%). The prevalence of a history of catheter ablation of AF was significantly higher in the high efficacy group than in the low efficacy group (73.0% vs. 44.0%, p = .048) and was the only independent predictor of high rATP efficacy (odds ratio, 3.45; p = .038). The rATP success rate in patients with (n = 30) and without (n = 21) a history of catheter ablation was 53.9% (40.0%-67.5%) and 36.4% (22.2%-47.7%), respectively (p = .012). The effect of rATP after ablation was more pronounced in patients with long cycle length episodes (≥75% of AT/AF sequences having a cycle length of 200-449 ms) (67.3% [46.0%-73.6%] vs. 30.6% [18.1%-60.3%], p = .027). The high efficacy group had a significantly lower incidence of AT/AF lasting ≥1, ≥7, and ≥30 days than the low efficacy group.

Conclusion: rATP combined with catheter ablation therapy is effective in suppressing AT/AF.
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http://dx.doi.org/10.1111/jce.15551DOI Listing
July 2022

Chemometric evaluations of repeatability and detection limit in high-performance liquid chromatography with electrochemical detection.

J Chromatogr A 2022 Jun 17;1673:463075. Epub 2022 Apr 17.

School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

The function of mutual information (FUMI) theory proposes that it is possible to obtain a relative standard deviation (RSD) of the peak area of an analyte from baseline noises and a signal on a single chromatogram when the analyte concentrations are proportional to their peak areas. In this study, we demonstrate that the FUMI theory using noise parametrization by the difference method is applicable for the evaluations of repeatability and detection limit (DL) in high-performance liquid chromatography with electrochemical detection (HPLC-ECD). HPLC-ECD for determining vincristine (VCR) was taken as an example, and VCR was detected on a glassy carbon surface at +0.8 V vs. Ag/AgCl. In the comparisons of precision profiles (plots of RSD of peak area against concentrations of an analyte), the stochastically estimated RSD (N = 1) by the FUMI theory fell within the 95% confidence intervals of statistically estimated RSD (N = 6) by repetitive measurements. Furthermore, the DL obtained by the FUMI theory (3.3×SD) was almost the same value as that by the signal-to-noise ratio (S/N) = 3. Moreover, we introduced a manual method for signal-noise resolution to obtain noise parameters from a chromatogram with low-pass Bessel filter processing. In conclusion, our results show that the FUMI theory using noise parametrization by the difference method can be applied to the evaluations of repeatability and DL in HPLC-ECD without and with a low-pass Bessel filter.
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http://dx.doi.org/10.1016/j.chroma.2022.463075DOI Listing
June 2022

Benefit of veno-arterial extracorporeal membrane oxygenation combined with Impella (ECpella) therapy in acute coronary syndrome with cardiogenic shock.

J Cardiol 2022 08 12;80(2):116-124. Epub 2022 Mar 12.

Department of Cardiac and Vascular Surgery, Dokkyo Medical University School of Medicine, Mibu, Japan.

Background: Patients with acute coronary syndrome complicated with cardiogenic shock (ACS-CS) frequently require mechanical circulatory support. In addition to veno-arterial extracorporeal membrane oxygenation (VA-ECMO), use of the Impella® (ECpella) (Abiomed Inc., Danvers, MA, USA) heart pump may improve the prognosis of such patients. In this study, we compared the efficacy of VA-ECMO plus intra-aortic balloon pumping (ECMO-IABP) with that of the ECpella for add-on circulatory support of VA-ECMO.

Methods: Clinical outcomes of 64 patients with ACS-CS treated with ECMO-IABP (n = 41) or ECpella (n = 23) between January 2013 and April 2021 were retrospectively analyzed. The primary outcomes were 30-day and 365-day mortality. In addition, patients resuscitated after cardiopulmonary arrest (CPA) were evaluated separately.

Results: The ECpella group showed significantly lower mid-term mortality than the ECMO-IABP group [30-day mortality (39.1% vs 56.1%, respectively; p = 0.193) and 365-day mortality (43.5% vs 75.6%, respectively; p = 0.010)], with significantly higher rates of new hemodialysis and bleeding at the vascular access site. Also, among the limited number of patients resuscitated from CPA, mortality was significantly lower in the ECpella group than the ECMO-IABP group [30-day mortality (28.6% vs 65.4%, respectively; p = 0.026) and 365-day mortality (28.6% vs 84.6%, respectively; p < 0.001)]. Among the resuscitated patients, ECMO weaning period and the incidence of neurological complications were related to 30-day mortality; The incidence of neurological complications was related to 365-day mortality. The use of ECpella was strongly associated with both 30-day and 365-day survival.

Conclusions: The ECpella heart pump may provide a survival advantage over ECMO-IABP in patients with ACS-CS.
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http://dx.doi.org/10.1016/j.jjcc.2022.02.013DOI Listing
August 2022

Effects of sampling rate and noise filter processing on repeatability assessment in UHPLC with ultraviolet detection based on the ISO 11843-7.

Anal Sci 2022 Jan 28;38(1):183-189. Epub 2022 Feb 28.

School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

The present study examines whether short measurement time and noise filter processing in an ultra-high-performance liquid chromatography with ultraviolet detection (UHPLC-UV) contribute to limitations for repeatability assessment based on the ISO 11843 part 7 (ISO 11843-7), which can stochastically provide a measurement standard deviation (SD) caused by baseline noise (S). In this study, ergosterol was used as an example in UHPLC-UV analysis. From the results of power spectrum analysis of baseline noise, 1024 consecutive digital data points provided a suitable S. Thus, it was found that an S can be obtained from about 1 min of baseline when a chromatogram was recorded at sampling rate of 20 points s in the present UHPLC-UV system. The relative SDs (RSDs) of the peak area obtained by the ISO 11843-7 were within 95% of the confidential intervals of the RSDs obtained by repetitive measurements, indicating the ISO 11843-7 is applicable to estimate repeatability in a UHPLC-UV system. In a similar way, we found that the RSD of the peak area obtained from a chromatogram with noise filter processing in UHPLC-UV could also be estimated by the ISO 11843-7. In conclusion, we experimentally demonstrate that short measurement time and noise filter processing are not limitations for repeatability assessment based on the ISO 11843-7.
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http://dx.doi.org/10.2116/analsci.21P259DOI Listing
January 2022

Digital-optical computational imaging capable of end-point logic operations.

Opt Express 2022 Jan;30(1):210-221

In this study, digital-optical computational imaging is proposed for object data transmission with a capability to achieve end-point logic operations over free-space data transmission. The framework is regarded as an extension of computational imaging using digital-optical codes originally developed for digital optical computing. Spatial code patterns for optical logic operations are extended to digital-optical codes in the temporal and spectral domains. The physical form of the digital-optical codes is selected, as appropriate, for the situation in use, and different forms can be combined to increase the data-transmission bandwidth. The encoded signals are transferred over free space and decoded by a simple procedure on the destination device, thus enabling logic operations at the end-point of the data transmission. To utilize the benefits of digital processing, a data-transfer mode is introduced which assigns preprocessing for the signals to be encoded and the end-point processing. As a demonstration of the proposed method, an experimental testbed was constructed assuming data transmission from sensor nodes to a gateway device appearing in the Internet of Things. In the experiment, encrypted signals of the sensor nodes, which were encoded by spatial digital-optical codes on RGB channels, were captured as an image, and the original signals were retrieved correctly by an end-point exclusive OR operation.
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http://dx.doi.org/10.1364/OE.442985DOI Listing
January 2022

[From Cure to Care: Career Path to a Domiciliary Doctor].

Authors:
Ryo Watanabe

Brain Nerve 2022 Jan;74(1):51-54

Watanabe Clinic.

A neurologist who specializes in home-based medicine attends not only to the patient's diseases, such as ALS and Parkinson's disease, but also to the whole patient and their needs in daily life and family relationship. Neurologists are also required not only to have diagnostic and therapeutic capacity but also to have sustained commitment to see the patient and family with empathy until the end. To achieve this, they must take on the leadership role of the multidisciplinary team.
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http://dx.doi.org/10.11477/mf.1416201978DOI Listing
January 2022

cGMP signaling pathway that modulates NF-κB activation in innate immune responses.

iScience 2021 Dec 18;24(12):103473. Epub 2021 Nov 18.

Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.

The nuclear factor-kappa B (NF-κB) pathway is an evolutionarily conserved signaling pathway that plays a central role in immune responses and inflammation. Here, we show that NF-κB signaling is activated via a pathway in parallel with the Toll receptor by receptor-type guanylate cyclase, Gyc76C. Gyc76C produces cyclic guanosine monophosphate (cGMP) and modulates NF-κB signaling through the downstream Tollreceptor components dMyd88, Pelle, Tube, and Dif/Dorsal (NF-κB). The cGMP signaling pathway comprises a membrane-localized cGMP-dependent protein kinase (cGK) called DG2 and protein phosphatase 2A (PP2A) and is crucial for host survival against Gram-positive bacterial infections in . A membrane-bound cGK, PRKG2, also modulates NF-κB activation via PP2A in human cells, indicating that modulation of NF-κB activation in innate immunity by the cGMP signaling pathway is evolutionarily conserved.
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http://dx.doi.org/10.1016/j.isci.2021.103473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710550PMC
December 2021

Correction to: Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population.

J Hum Genet 2022 Apr;67(4):245

Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

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http://dx.doi.org/10.1038/s10038-021-00997-9DOI Listing
April 2022

Brønsted acid-induced transannulation of the phytochemical zerumbone.

Org Biomol Chem 2021 12 8;19(47):10444-10454. Epub 2021 Dec 8.

Major in Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nara, Nara 631-8505, Japan.

The sesquiterpene zerumbone was treated with HCl in ethyl acetate under the light-protected condition, and the time-dependent conversions were analyzed by gas chromatography. Nine products were isolated, and their structures were revealed by several NMR measurements such as H NMR, C{H} NMR, distortionless enhancement by polarization transfer (DEPT)-135, H-H correlation spectroscopy (COSY), H-C heteronuclear multiple quantum coherence (HMQC), and H-C heteronuclear multiple bond coherence (HMBC). The X-ray crystallography determined the stereochemistries of the three products and the two derivatives. After all, this acidic reaction was found to provide the (2,6,10)-isomer, the two HCl adducts, the two 7,6-bicyclic compounds, the valence isomers cycloheptatriene and norcaradiene, and the two dihydronaphthalenes. Based on the product analyses of the reactions from the isolated intermediates as well as the mechanistic considerations, these products were arranged into two paths: one of the paths ended in the two dihydronaphthalenes the same as previously reported under the Lewis acid condition; the other ended in the 7,6-bicyclic compound, the epimer of which was known. In addition, density functional theory (DFT) calculations indicated that the (2,6,10)-isomer was more stable than the (2,6,10)-isomer as well as that the activation energy for the isomerization at the C2-C3 double bond decreased to half by protonation. The closely examined reaction mechanisms under the simple acidic condition were established upon the intensive characterization of the intermediates and products, and these findings would add to the attractive value of zerumbone and would help understand the unknown biosynthetic pathway around sesquiterpenoids.
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http://dx.doi.org/10.1039/d1ob01634bDOI Listing
December 2021

Spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers.

Opt Express 2021 Nov;29(24):39096-39106

To realize simplified cost-efficient optical networks with routing flexibility and scaling potential, a spatial-light-modulator-based optical-fiber joint switch for few-mode multicore fibers is proposed herein, which can route all spatial channels together as a unit. Numerical simulations and experiments were performed, and the results show that the signal paths for a 6-mode 19-core fiber can be simultaneously switched to the target output ports using the proposed method, and the mode-field patterns of the diffracted light can be maintained after joint switching. Further, the maximum port crosstalk can be reduced considerably from -11.6 to -25.1 dB by changing the position of the output port in the proposed method.
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http://dx.doi.org/10.1364/OE.443033DOI Listing
November 2021

Forensic evaluation of fatal-suffocating retropharyngeal haematoma secondary to cervical fractures: Report of two cases.

J Forensic Leg Med 2022 Jan 15;85:102274. Epub 2021 Nov 15.

Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Purpose: Traumatic retropharyngeal haematoma, a condition of low incidence, often occurs secondary to cervical injuries. Owing to the adjacent anatomical location and its insidious formation, retropharyngeal haematoma is prone to cause airway obstruction, which can occasionally be fatal. Though well known in clinical practice, retropharyngeal haematomas are rarely encountered in forensic practice and are not sufficiently explored from a forensic perspective.

Case Presentation: Herein, we present two cases of fatal-suffocating retropharyngeal haematoma following cervical vertebral fractures. In both cases, the time from injury to death was evident, showing unusually long periods from injury to death, specifically 4 days and 2 days, respectively. The causes of death were illustrated, and the delayed onset of fatal airway obstruction was explained. The important points regarding autopsies suspected to be fatal traumatic retropharyngeal haematomas were discussed.

Conclusions: Knowledge of the possibility of late onset and understanding of the features of imaging and autopsy findings of traumatic retropharyngeal haematoma is beneficial for forensic pathologists dealing with similar cases.
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http://dx.doi.org/10.1016/j.jflm.2021.102274DOI Listing
January 2022

Efficacy of His Bundle Pacing on LV Relaxation and Clinical Improvement in HF and LBBB.

JACC Clin Electrophysiol 2022 01 25;8(1):59-69. Epub 2021 Aug 25.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: This study aimed to compare acute hemodynamic improvements and responses to His bundle pacing (HBP) and conventional biventricular pacing (BVP).

Background: HBP can correct left bundle branch block (LBBB) and may be an alternative cardiac resynchronization therapy (CRT) to BVP.

Methods: Fourteen consecutive patients with heart failure (HF) and typical LBBB who required CRT were enrolled. The acute hemodynamic responses during HBP and BVP were compared using a micromanometer-tipped catheter inserted into the left ventricle (LV) before CRT. Each configuration was compared with AAI mode. A permanent HBP device was implanted when LBBB correction threshold was ≤1.5 V at 1.0 ms, and remaining patients were treated with BVP. Clinical and echocardiographic improvements were assessed during a 12-month follow-up period.

Results: The LV contractile index (positive maximal rate of LV pressure rise [dP/dt]) increased similarly during HBP and BVP (18.8% ± 6.4% vs 18.0% ± 10.2%; P = 0.810). LV relaxation indices (negative dP/dt and tau) were significantly improved during HBP compared with BVP (negative dP/dt: 14.3% ± 5.5% vs 3.1% ± 8.1%; P < 0.001; tau: 7.2% ± 4.3% vs -0.8% ± 8.1%; P = 0.001). Nine (64%) patients received permanent HBP devices, while 5 patients were treated with BVP. The New York Heart Association functional class, LV ejection fraction, LV end-systolic volume, and B-type natriuretic peptide level improved in patients treated with HBP and BVP (all P < 0.05 vs baseline). Patients treated with HBP exhibited earlier and greater improvements of the LV ejection fraction and LV end-systolic volume than did those with BVP.

Conclusions: HBP improves systolic function and LV relaxation in patients with HF and LBBB. CRT via HBP produced earlier and greater clinical responses than BVP.
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http://dx.doi.org/10.1016/j.jacep.2021.06.011DOI Listing
January 2022

Natural Kaolin-Based Ni Catalysts for CO Methanation: On the Effect of Ce Enhancement and Microwave-Assisted Hydrothermal Synthesis.

ACS Omega 2021 Jun 18;6(21):13779-13794. Epub 2021 May 18.

Department of Chemical Engineering, Faculty of Engineering, Mahidol University, Nakhon Pathom 73170, Thailand.

Natural kaolin-based Ni catalysts have been developed for low-temperature CO methanation. The catalysts were prepared via a one-step co-impregnation of Ni and Ce onto a natural kaolin-derived metakaolin using a microwave-assisted hydrothermal method as an acid-/base-free synthesis method. The influences of microwave irradiation and Ce promotion on the catalytic enhancement including the CO conversion, CH selectivity, and CH yield were experimentally investigated by a catalytic test of as-prepared catalysts in a fixed-bed tubular reactor. The relationship between the catalyst properties and its methanation activities was revealed by various characterization techniques including X-ray fluorescence, X-ray diffraction, Brunauer-Emmett-Teller, scanning electron microscopy, selected area electron diffraction, transmission electron microscopy, elemental mapping, H temperature-programmed reduction, and X-ray absorption near-edge structure analyses. Among the two enhancement methods, microwave and Ce promotion, the microwave-assisted synthesis could produce a catalyst containing highly dispersed Ni particles with a smaller Ni crystallite size and higher catalyst reducibility, resulting in a higher CO conversion from 1.6 to 7.5% and a better CH selectivity from 76.3 to 79.9% at 300 °C. Meanwhile, the enhancement by Ce addition exhibited a great improvement on the catalyst activities. It was experimentally found that the CO conversion increased approximately 7-fold from 7.5 to 52.9%, while the CH selectivity significantly improved from 79.9 to 98.0% at 300 °C. Though the microwave-assisted synthesis could further improve the catalyst activities of Ce-promoted catalysts, the Ce addition exhibited a more prominent impact than the microwave enhancement. Cerium oxide (CeO) improved the catalyst activities through mechanisms of higher CO adsorption capacity with its basic sites and the unique structure of CeO with a reversible valence change of Ce and Ce and high oxygen vacancies. However, it was found that the catalyst prepared by microwave-assisted synthesis and Ce promotion proved to be the optimum catalyst in this study. Therefore, the present work demonstrated the potential to synthesize a nickel-based catalyst with improved catalytic activities by adding a small amount of Ce as a catalytic promoter and employing microwave irradiation for improving the Ni dispersion.
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http://dx.doi.org/10.1021/acsomega.1c01231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173562PMC
June 2021

Diagnosis by forensic autopsy of cannula malposition resulting in fatal tension pneumothorax after attempted percutaneous tracheostomy: A short communication.

J Forensic Leg Med 2021 Jul 6;81:102177. Epub 2021 May 6.

Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Percutaneous tracheostomy is commonly performed in the emergency department or intensive care unit to secure the airways of patients. This procedure is associated with a low incidence of complications; however, some of them, such as iatrogenic pneumothorax, can be fatal. Pneumothorax after percutaneous tracheostomy is most often caused by perforation of the tracheal wall or malposition of the cannula. A woman in her 80s was referred to the emergency department owing to persistent and prolonged coughing. Having speculated that she had acute epiglottitis, and having failed to achieve oral tracheal intubation, the physician performed a percutaneous tracheostomy to secure her airway. However, progressive percutaneous emphysema developed immediately thereafter, and the patient died shortly. Postmortem computed tomography showed bilateral pneumothorax. Forensic autopsy revealed that the tracheostomy cannula had failed to reach the trachea and was erroneously inserted into the right thoracic cavity via peritracheal route. Thus, it was determined that the patient's death was attributable to tension pneumothorax caused by cannula malposition during attempted tracheostomy. To the best of our knowledge, this is the first forensic autopsy case report on fatal tension pneumothorax caused by attempted percutaneous tracheostomy.
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http://dx.doi.org/10.1016/j.jflm.2021.102177DOI Listing
July 2021

Single-Round DNA Aptamer Selection by Combined Use of Capillary Electrophoresis and Next Generation Sequencing: An Aptaomics Approach for Identifying Unique Functional Protein-Binding DNA Aptamers.

Chemistry 2021 Jul 10;27(39):10058-10067. Epub 2021 Jun 10.

Graduate School of Science and Engineering, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama, 338-8570, Japan.

In DNA aptamer selection, existing methods do not discriminate aptamer sequences based on their binding affinity and function and the reproducibility of the selection is often poor, even for the selection of well-known aptamers like those that bind the commonly used model protein thrombin. In the present study, a novel single-round selection method (SR-CE selection) was developed by combining capillary electrophoresis (CE) with next generation sequencing. Using SR-CE selection, a successful semi-quantitative and semi-comprehensive aptamer selection for thrombin was demonstrated with high reproducibility for the first time. Selection rules based on dissociation equilibria and kinetics were devised to obtain families of analogous sequences. Selected sequences of the same family were shown to bind thrombin with high affinity. Furthermore, data acquired from SR-CE selection was mined by creating sub-libraries that were categorized by the functionality of the aptamers (e. g., pre-organized aptamers versus structure-induced aptamers). Using this approach, a novel fluorescent molecular recognition sensor for thrombin with nanomolar detection limits was discovered. Thus, in this proof-of-concept report, we have demonstrated the potential of a "DNA Aptaomics" approach to systematically design functional aptamers as well as to obtain high affinity aptamers.
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http://dx.doi.org/10.1002/chem.202100177DOI Listing
July 2021

Identification of OPN3 as associated with non-syndromic oligodontia in a Japanese population.

J Hum Genet 2021 Aug 20;66(8):769-775. Epub 2021 Feb 20.

Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Tooth agenesis is one of the most frequent congenital abnormalities found in the maxillofacial region. Oligodontia, a severe form of tooth agenesis, occurs as an isolated anomaly or as a syndromic feature. We performed whole exome sequencing analyses to identify causative mutation in a Japanese family with three affected individuals with non-syndromic oligodontia. After variant filtering procedures and validation by Sanger sequencing, we identified one missense mutation (c.668 C > T, p.Gly223Asp) in OPN3 at 1q43, encoding a photosensitive G-protein-coupled receptor (GPCR) expressed in various tissues including brain, liver, and adipose. This mutation was predicted to be pathogenic in silico and was not found in the public databases. We further examined 48 genetically unrelated cases by targeted sequencing of the OPN3 gene region and found one additional missense variant in this gene (c.768 C > T, p.Met256Ile) that was also predicted to be pathogenic. Localization of OPN3 protein by immunohistochemical analysis using mouse embryo revealed its specific expression in the tooth gems from bud to bell stages and their surrounding tissues. These results indicated that OPN3 was involved in non-syndromic oligodontia, which has made an anchoring point for clinical application including DNA diagnostics.
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http://dx.doi.org/10.1038/s10038-021-00903-3DOI Listing
August 2021

The 3 × 120° rotary mechanism of F-ATPase is different from that of the bacterial and mitochondrial F-ATPases.

Proc Natl Acad Sci U S A 2020 11 9;117(47):29647-29657. Epub 2020 Nov 9.

Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, 113-8656 Tokyo, Japan;

The rotation of F-ATPase (PdF) was studied using single-molecule microscopy. At all concentrations of adenosine triphosphate (ATP) or a slowly hydrolyzable ATP analog (ATPγS), above or below , PdF showed three dwells per turn, each separated by 120°. Analysis of dwell time between steps showed that PdF executes binding, hydrolysis, and probably product release at the same dwell. The comparison of ATP binding and catalytic pauses in single PdF molecules suggested that PdF executes both elementary events at the same rotary position. This point was confirmed in an inhibition experiment with a nonhydrolyzable ATP analog (AMP-PNP). Rotation assays in the presence of adenosine diphosphate (ADP) or inorganic phosphate at physiological concentrations did not reveal any obvious substeps. Although the possibility of the existence of substeps remains, all of the datasets show that PdF is principally a three-stepping motor similar to bacterial vacuolar (V)-ATPase from This contrasts with all other known F-ATPases that show six or nine dwells per turn, conducting ATP binding and hydrolysis at different dwells. Pauses by persistent Mg-ADP inhibition or the inhibitory ζ-subunit were also found at the same angular position of the rotation dwell, supporting the simplified chemomechanical scheme of PdF Comprehensive analysis of rotary catalysis of F from different species, including PdF, suggests a clear trend in the correlation between the numbers of rotary steps of F and F domains of F-ATP synthase. F motors with more distinctive steps are coupled with proton-conducting F rings with fewer proteolipid subunits, giving insight into the design principle the FF of ATP synthase.
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http://dx.doi.org/10.1073/pnas.2003163117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703542PMC
November 2020

Simultaneous Measurements of Photoabsorption and Photoelectrochemical Performance for Thickness Optimization of a Semiconductor Photoelectrode.

ACS Comb Sci 2020 12 22;22(12):791-795. Epub 2020 Oct 22.

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-ku, Kitakyushu 808-0196, Japan.

We established a system for simultaneous measurements of photoelectrochemical (PEC) reaction and photoabsorption in a semiconductor photoelectrode. This system uses a photoacoustic technique and photoelectrodes with a film-thickness gradient that was prepared by electrophoretic deposition of tungsten(VI) oxide particles while pulling up a substrate. The system enabled high-throughput determination of optimum film thickness, and the results showed that irradiation direction has a significant influence on PEC performance for a photoelectrode with a thick film. Furthermore, the mechanism of enhancement of PEC performance by postnecking treatment was discussed.
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http://dx.doi.org/10.1021/acscombsci.0c00113DOI Listing
December 2020

Autopsy Identification of Viable Mycobacterium Tuberculosis in the Lungs of a Markedly Decomposed Body.

J Forensic Sci 2020 Nov 31;65(6):2194-2197. Epub 2020 Aug 31.

Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Various infectious diseases, including COVID-19, MERS, and tuberculosis, are global public health issues. Tuberculosis, which is caused by Mycobacterium tuberculosis (MTB), is highly contagious and can be transmitted through inhalation of the bacteria. However, it has been assumed that the infectiousness of bacteria and viruses in dead bodies weakens as the time from death increases. In particular, there is little awareness of infection control measures concerning decomposed bodies or even the need for such measures. The deceased, in whom we discovered MTB 3 months following her death, was a woman in her 80s who died at home. We performed judicial autopsy, because police suspected homicide when her husband hanged himself. Obtained organs were used for microscopic examination by hematoxylin-eosin staining and Ziehl-Neelsen staining. In addition, real-time PCR and mycobacterial culture testing using Ogawa's medium were performed for the detection of MTB. We found that the MTB in the decomposed body remained viable and potentially infectious. To identify the bacterial strain further, we performed DNA-DNA hybridization and identified the strain as MTB complex. Potentially infectious live MTB survived in the dead body far longer than had been previously reported. Pathologists should consider microbial culture tests for all autopsied cases in which the decedent's medical history or macro-examination suggests possible infection, even when a long duration of time has passed since death. Pathologists and specialists who perform autopsies should recognize that all dead bodies are potentially infectious, including those in which long periods have elapsed since death.
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http://dx.doi.org/10.1111/1556-4029.14532DOI Listing
November 2020

Open-label, multicenter, dose-titration study to determine the efficacy and safety of tolvaptan in Japanese patients with hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone.

Endocr J 2021 Jan 29;68(1):17-29. Epub 2020 Aug 29.

Department of Endocrinology and Metabolism, International University of Health and Welfare Hospital, Tochigi, Japan.

The purpose of this study was to determine the efficacy and safety of tolvaptan in Japanese patients with hyponatremia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This multicenter, open-label, dose-escalation, phase III study enrolled Japanese patients (20-85 years old) with hyponatremia secondary to SIADH who were unresponsive to fluid restriction. Oral tolvaptan was administered for up to 30 days, initially at 7.5 mg/day, but escalated daily as necessary, based on the serum sodium concentration and safety, over the first 10 days until the optimal maintenance dose was determined for each patient (maximum 60 mg/day). The primary endpoint was the proportion of patients with normalized serum sodium concentration on the day after the final tolvaptan dose. Secondary endpoints included the mean change in serum sodium concentration from baseline on the day after the final dose. Sixteen patients (male, 81.3%; mean ± standard deviation age 71.9 ± 6.1 years) received tolvaptan treatment and 11 patients completed the study with one patient re-administered tolvaptan in the treatment period. Serum sodium concentrations normalized in 13 of 16 (81.3%) patients on the day after the final tolvaptan dose. The mean change in serum sodium concentration from baseline on the day after the final dose was 11.0 ± 4.3 mEq/L. Adverse events considered related to tolvaptan (10 [62.5%] patients) were generally of mild to moderate severity. Oral tolvaptan corrects hyponatremia in Japanese patients with SIADH with a similar efficacy and safety profile as that noted in non-Japanese patients.
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http://dx.doi.org/10.1507/endocrj.EJ20-0216DOI Listing
January 2021

Dipeptidyl Peptidase-4 Inhibitor Reduces the Risk of Developing Hypertrophic Scars and Keloids following Median Sternotomy in Diabetic Patients: A Nationwide Retrospective Cohort Study Using the National Database of Health Insurance Claims of Japan.

Plast Reconstr Surg 2020 07;146(1):83-89

From the Department of Diabetes, Metabolism, Endocrinology, Rheumatology, and Collagen Diseases and the Department of Plastic and Reconstructive Surgery, General Informatics Division, Tokyo Medical University; and the Kanagawa University of Human Services, Faculty of Health and Social Services.

Background: Hypertrophic scars and keloids, which are abnormalities of fibrosis, often occur in surgical wounds; however, their exact cause and preventive measures are unknown. The administration of dipeptidyl peptidase-4 inhibitors to humans is expected to suppress fibrosis in wounds and minimize hypertrophic scar and keloid formation.

Methods: This study aimed to verify the suppressive effect of dipeptidyl peptidase-4 inhibitors on the formation of hypertrophic scars or keloids using real world data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. It is a retrospective cohort study, and data were extracted from the National Database between April of 2013 and March of 2015. Patients who underwent median sternotomy were included in the study based on their claimed surgical codes. Subjects who were prescribed dipeptidyl peptidase-4 inhibitors constituted the treatment group; subjects who were not prescribed or administered dipeptidyl peptidase-4 inhibitors during that period constituted the nontreatment group.

Results: Subjects included 5430 patients throughout Japan (3509 men and 1921 women). Of the 446 subjects who were treated with dipeptidyl peptidase-4 inhibitors within 1 year before the procedure, fewer than 10 (<2 percent) developed either hypertrophic scars or keloids. Of the 4984 subjects who were not treated, 152 (3.05 percent) were at significantly lower risk for hypertrophic scars and keloids (p = 0.04). A logistic regression analysis was performed to adjust for confounding factors, with history of hypertrophic scar formation as the explained variable.

Conclusion: This study revealed that dipeptidyl peptidase-4 inhibitors suppress the onset of hypertrophic scars or keloids after surgery in humans.

Clinical Question/level Of Evidence: Therapeutic, III.
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http://dx.doi.org/10.1097/PRS.0000000000006904DOI Listing
July 2020

Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells.

EMBO J 2020 04 3;39(7):e103949. Epub 2020 Mar 3.

Isotope Science Center, The University of Tokyo, Tokyo, Japan.

Histone H3 lysine-9 di-methylation (H3K9me2) and lysine-27 tri-methylation (H3K27me3) are linked to repression of gene expression, but the functions of repressive histone methylation dynamics during inflammatory responses remain enigmatic. Here, we report that lysine demethylases 7A (KDM7A) and 6A (UTX) play crucial roles in tumor necrosis factor (TNF)-α signaling in endothelial cells (ECs), where they are regulated by a novel TNF-α-responsive microRNA, miR-3679-5p. TNF-α rapidly induces co-occupancy of KDM7A and UTX at nuclear factor kappa-B (NF-κB)-associated elements in human ECs. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and are both required for activation of NF-κB-dependent inflammatory genes. Chromosome conformation capture-based methods furthermore uncover increased interactions between TNF-α-induced super enhancers at NF-κB-relevant loci, coinciding with KDM7A and UTX recruitments. Simultaneous pharmacological inhibition of KDM7A and UTX significantly reduces leukocyte adhesion in mice, establishing the biological and potential translational relevance of this mechanism. Collectively, these findings suggest that rapid erasure of repressive histone marks by KDM7A and UTX is essential for NF-κB-dependent regulation of genes that control inflammatory responses of ECs.
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http://dx.doi.org/10.15252/embj.2019103949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110136PMC
April 2020
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