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BACKGROUND: Suprahyoid muscles behavior during the tongue lifting movement has not yet been elucidated. OBJECTIVE: The purpose of this study was to investigate the potential of elastography imaging to examine developmental oral dysfunction in children and oral hypofunction in older adults using sonography. METHODS: Tongue pressure was measured using a manometer with a probe. The tongue pressure was measured with simultaneously scanning the geniohyoid muscle (GHM) and the anterior belly of the digastric muscle (DGM) using sonographic elastography. Sagittal images of the GHM and coronal images of the DGM were used for the strain ratio measurement. The strain ratio of the muscles was measured three times for each subject with the tongue pressure values of 0–30 kPa. RESULTS: The strain ratio of the GHM were higher than those of the DGM at tongue pressure of 10, 20 and 30 kPa. The strain ratio of the GHM increased as the tongue pressure increased in all participants. In contrast, the strain ratio of the DGM tended to slowly decrease as tongue pressure increased in female participants. CONCLUSION: Sonographic elastography is useful for visual and quantitative evaluation of elastic properties in suprahyoid muscles during tongue lifting movements.

Clinically mild encephalitis/encephalopathy with reversible splenial lesions (MERS) is a mild form of encephalitis/encephalopathy that appears in association with various conditions, including infection. COVID-19 is also known to cause MERS. MERS more commonly occurs in children, and adult cases are relatively rare. Typical head MRI findings include a round lesion in the mid-layer of the corpus callosum with a high signal intensity on diffusion-weighted images. Most improve within a week. Although the exact mechanism by which the cerebral corpus callosum is affected is still unknown, several hypotheses have been proposed, including the involvement of electrolyte abnormalities (e.g., hyponatremia) and inflammatory cytokines (e.g., IL-6). In this report, we describe the first case of COVID-associated MERS with a typical imaging course and hyponatremia, with a review of the relevant literature. When psychiatric symptoms and the disturbance of consciousness appear in COVID patients, MERS should be considered in addition to delirium due to fever and hypoxia.

Background: The mechanism underlying the sex differences in atrial fibrillation (AF) recurrence following pulmonary vein (PV) isolation is not fully understood. We hypothesized that non-PV foci and epicardial adipose tissue (EAT) play a key role. Methods and Results: Data from 304 consecutive patients (75% males) who underwent contrast-enhanced computed tomography and catheter ablation of AF were reviewed. The EAT around the atrium was measured separately in 4 parts of the atrium. All patients underwent high-dose isoproterenol infusions to assess the non-PV foci. Significantly more non-PV foci and less EAT around the atrium were observed in female patients than in male patients. In males, those with non-PV foci on the left atrial (LA) anterior wall had significantly greater EAT for the same lesions than those without non-PV foci. During a median follow-up of 27 months, the predictors of AF recurrence after first catheter ablation were female sex, presence of non-PV foci, LA diameter, and septal EAT index. A sex-specific analysis revealed that LA diameter was a predictor only in males and that the presence of non-PV foci in the septal region was a strong predictor in males (hazard ratio [HR]: 2.24) and females (HR: 3.65). Conclusions: Sex-specific differences were observed in non-PV foci sites and local EAT and in regard to the predictors of AF recurrence.

Background: Ventricular tachycardia (VT) non-inducibility at the end of ablation is associated with a less likely VT recurrence. However, it is not clear whether we should use VT non-inducibility as a routine end point of VT ablation. The aim of this study was to evaluate VT recurrence in patients in whom VT non-inducibility was not achieved at the end of the RF ablation and the factors attributing to the VT recurrence.Methods: We analyzed 62 patients in whom VT non-inducibility was not achieved at the end of the RF ablation were studied.Results: Over 2 years, 22 (35%) of the cases had VT recurrences. A multivariate analysis showed that an LVEF≥35% (HR:0.19; 95% CI:0.06- 0.49; PConclusion: Even if VT non-inducibility was not achieved, patients with an LVEF≥35% or in whom partial success could be achieved might be prevented from having VT recurrences. The validity of the VT non-inducibility of any VT should be evaluated considering each patient’s background and the results of the procedure.

The skin overlying cardiovascular implantable electronic devices (CIEDs) sometimes becomes very thin after implantations, which could cause a device erosion. The factors related to the skin thickness of device pockets have not been elucidated. This study aimed to evaluate the skin thickness of CIED pockets and search for the factors associated with the thickness.Seventeen skin thickness points around the CIED pocket were measured through ultrasonography in each patient.A total of 101 patients (76 ± 11 years, 26 female) were enrolled. The median duration from the implantation to the examination was 95 months (quartile: 52.5-147.5). The median skin thickness overlying the device was 4.1 mm (3.3-5.9). Patients with heart failure and malignancy had thinner skin overlying the CIED than those without. A significant correlation existed between skin thickness and body mass index (BMI), hemoglobin, serum creatinine, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction. In contrast, age, gender, and device size did not exhibit a significant correlation with skin thickness. A multivariate logistic regression analysis revealed that chronic heart failure and a decrease in the eGFR and BMI were independent predictive factors of "very thin (≦3.3 mm)" skin of the CIED pocket late after an implantation.Aside from a low BMI, the comorbidities (low hemoglobin, heart failure, and renal dysfunction) had a stronger impact on the skin thickness overlying the device than the device size. A careful observation of the device pocket should be performed in patients with those risk factors.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which there are several variants. The three major variants (Alpha, Delta, and Omicron) carry the N501Y, L452R, and Q493R/Q498R mutations, respectively, in the S gene. Control of COVID-19 requires rapid and reliable detection of not only SARS-CoV-2 but also its variants. We previously developed a reverse transcription loop-mediated isothermal amplification assay combined with a bioluminescent assay in real time (RT-LAMP-BART) to detect the L452R mutation in the SARS-CoV-2 spike protein. In this study, we established LAMP primers and peptide nucleic acid probes to detect N501Y and Q493R/Q498R. The LAMP primer sets and PNA probes were designed for the N501Y and Q493R/Q498R mutations on the S gene of SARS-CoV-2. The specificities of RT-LAMP-BART assays were evaluated using five viral and four bacterial reference strains. The sensitivities of RT-LAMP-BART assays were evaluated using synthetic RNAs that included the target sequences, together with RNA-spiked clinical nasopharyngeal and salivary specimens. The results were compared with those of conventional real-time reverse transcription-polymerase chain reaction (RT-PCR) methods. The method correctly identified N501Y and Q493R/Q498R. Within 30 min, the RT-LAMP-BART assays detected up to 100–200 copies of the target genes; conventional real-time RT-PCR required 130 min and detected up to 500–3000 copies. Surprisingly, the real-time RT-PCR for N501Y did not detect the BA.1 and BA.2 variants (Omicron) that exhibited the N501Y mutation. The novel RT-LAMP-BART assay is highly specific and more sensitive than conventional real-time RT-PCR. The new assay is simple, inexpensive, and rapid; thus, it can be useful in efforts to identify SARS-CoV-2 variants of concern.

Background: Corticosteroids are widely used in patients with cardiac sarcoidosis (CS). In addition, upgrading to cardiac resynchronization therapy (CRT) is sometimes needed. This study aimed to investigate the impact of corticosteroid use on the clinical outcomes following CRT upgrades. Methods: A total of 48 consecutive patients with non-ischemic cardiomyopathies who underwent CRT upgrades were retrospectively reviewed and divided into three groups: group 1 included CS patients taking corticosteroids before the CRT upgrade (n = 7), group 2, CS patients not taking corticosteroids before the CRT upgrade (n = 10), and group 3, non-CS patients (n = 31). The echocardiographic response, heart failure hospitalizations, and cardiovascular deaths were evaluated. Results: The baseline characteristics during CRT upgrades exhibited no significant differences in the echocardiographic data between the three groups. After the CRT upgrade, responses regarding the ejection fraction (EF) and end-systolic volume (ESV) were significantly lower in CS patients than non-CS patients (ΔEF: group 1, 6.7% vs. group 2, 7.7% vs. group 3, 13.6%; p = .039, ΔESV: 3.0 ml vs. -12.7 ml vs. -37.2 ml; p = .008). The rate of an echocardiographic response was lowest in group 1 (29%). There were, however, no significant differences in the cumulative freedom from a composite outcome among the three groups (p = .19). No cardiovascular deaths occurred in group 1. Conclusion: The echocardiographic response to an upgrade to CRT and the long-term prognosis in patients with CS should be carefully evaluated because of the complex etiologies and impact of immunosuppressive therapy.

Coronavirus disease 2019 (COVID-19) is associated with fatal acute respiratory distress syndrome, which can be ameliorated by methylprednisolone pulse therapy, thereby reducing the risk of progression to respiratory failure and death. We aimed to determine the efficacy and safety of methylprednisolone pulse therapy for patients with COVID-19 pneumonia. In this retrospective, observational cohort study, seventy patients (age, 35–91 years) who were admitted to Saitama Medical University Hospital in Japan between March 2020 and January 2021 due to COVID-19 pneumonia were included. The difference in mortality between the methylprednisolone pulse therapy (n = 22) and dexamethasone therapy (n = 48) groups was the primary outcome. Between-group differences in the average length of intensive care unit stay, duration of invasive mechanical ventilation, and incidence of treatment-related adverse events were the secondary outcomes. The methylprednisolone pulse therapy group showed a significantly lower mortality rate (3.8% vs. 20.2%, p = 0.006) and increased survival rate compared with the dexamethasone therapy group (p = 0.044). Additionally, without statistical significance, the average length of intensive care unit stay tended to be shorter in the methylprednisolone pulse therapy group (11.5 ± 6.1 days) than in the dexamethasone therapy group (22.3 ± 23.1 days) (p = 0.793). The average duration of invasive mechanical ventilation also tended to be shorter in the methylprednisolone pulse therapy group (15.3 ± 10.1 vs. 28.8 ± 9.2 days, p = 0.120). There were no significant differences in the incidence of treatment-related serious adverse events between the two groups. In conclusion, methylprednisolone pulse therapy for patients with COVID-19 pneumonia significantly reduced mortality and increased the survival rate compared to conventional dexamethasone therapy.

Rapid evaluation of antimicrobial susceptibility is important in the treatment of nosocomial infections by Gram-negative bacteria, which increasingly carry carbapenemases and metallo-β-lactamases. We developed loop-mediated isothermal amplification (LAMP)-based assays for four β-lactamase genes (blaKPC, blaNDM-1, blaIMP-1 group, and blaVIM). The assays were evaluated using eight reference bacterial strains (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter bereziniae) harboring six β-lactamase genes. A total of 55 Gram-negative bacterial strains, including 47 clinical P. aeruginosa isolates, fully characterized by next-generation sequencing (NGS), were used to evaluate the LAMP assays. The results were compared to those of conventional PCR. The LAMP assays were able to detect as few as 10 to 100 copies of a gene, compared to 10 to 104 copies for conventional PCR. The LAMP assay detected four β-lactamase genes with a sensitivity similar to that using purified DNA as the template in DNA-spiked urine, sputum, and blood specimens. By contrast, the sensitivity of PCR was 1- to 100-fold lower with DNA-spiked clinical specimens. Therefore, the LAMP assays were proved to be an appropriate tool for the detection of four β-lactamases.

The sporadic E (Es) layer is an ionospheric layer with a high electron density and thin altitudinal thickness and appears at altitudes around 100 km. The density is sometimes so high that even VHF radio waves from the ground can be reflected and propagate beyond the radio horizon. It has been shown that aeronautical VHF navigation signals in the 108–118 MHz band can propagate beyond the radio horizon to cause potential interference. However, there has been little technique to monitor the Es layer in wide area. The fine structures of the Es layers which reflects the dynamics of the thermosphere has not been well understood yet. This study shows that the ROTI (rate of TEC index) map by utilizing dense GNSS observations is effective in detecting the Es layer at least in the daytime. The Es layer studies has a well-defined frontal structure, when ROTI values are mapped at the typical Es layer height (100 km). A methodology of detecting and characterizing the Es layer frontal structure without manual operation is developed by utilizing the Hough transformation, and the front direction and velocity are successfully derived. Utilizing the characteristics of the frontal structure, fine structures of the Es layer can be studied, and a couple of interesting features are found. However, this technique would not always be applicable. Application to a homogeneous Es layer and nighttime Es layer are challenging problems. Nevertheless, it is still very useful, and is suitable for automated real-time Es layer monitoring system in a wide area.

Herein, we describe the first total synthesis of cochlearol B, a meroterpenoid natural product featuring a 4/5/6/6/6-fused pentacyclic structure. Key steps, oxidative cyclization and subsequent intramolecular [2+2] photocycloaddition, which constructed the pentacyclic structure in highly stereoselective manner, allowed efficient access to cochlearol B with the longest linear sequence of 16 steps, and in 9 % overall yield. Single-crystal X-ray crystallographic analysis clearly confirmed the stereochemistry of cochlearol B.

A 67-year-old woman with a 2-day history of a fever, headache and disturbed consciousness was admitted to our hospital. Bacillus subtilis was isolated from both the cerebrospinal fluid and blood. She was cured by the administration of vancomycin. Next-generation sequencing identified the strain as B. subtilis var. natto, the same strain found in natto, which this patient ate daily. We suspected that some of the B. subtilis that caused the infection may have actually been B. subtilis var. natto.

Background: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. Methods: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. Findings: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p Interpretation: A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes.

Suprahyoid muscles behavior during the tongue lifting movement has not yet been elucidated.The purpose of this study was to investigate the potential of elastography imaging to examine developmental oral dysfunction in children and oral hypofunction in older adults using sonography.Tongue pressure was measured using a manometer with a probe. The tongue pressure was measured with simultaneously scanning the geniohyoid muscle (GHM) and the anterior belly of the digastric muscle (DGM) using sonographic elastography. Sagittal images of the GHM and coronal images of the DGM were used for the strain ratio measurement. The strain ratio of the muscles was measured three times for each subject with the tongue pressure values of 0-30 kPa.The strain ratio of the GHM were higher than those of the DGM at tongue pressure of 10, 20 and 30 kPa. The strain ratio of the GHM increased as the tongue pressure increased in all participants. In contrast, the strain ratio of the DGM tended to slowly decrease as tongue pressure increased in female participants.Sonographic elastography is useful for visual and quantitative evaluation of elastic properties in suprahyoid muscles during tongue lifting movements.

Background: Demand is growing for remote electrocardiogram (ECG) monitoring systems in the COVID-19 era in Japan. This study describes initial experiences with a small wireless ECG monitoring device and the utility of delivery via the postal service for outpatient care in Japan. Methods and Results: Long-term ECG monitoring following postal delivery of the small ECG device was evaluated in 25 patients. The patients had no difficulties with either the postal delivery or self-fitting and wearing the devices. A median of 57 h monitoring per patient was performed. Arrhythmic events were detected in 8 patients. Most patients were satisfied with both the ECG devices and postal delivery. Conclusions: Postal delivery of ECG devices could be used in clinical practice to achieve less or no in-person contact during the COVID-19 era.

Background A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy late-gadolinium enhancement (LGE) areas and play an important role in AF drivers. However, this was not validated in humans. Objective The purpose of this study was to evaluate the LGE area properties of AF rotors in patients with persistent AF. Methods A total of 287 segments in 15 patients with persistent AF (longstanding persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). The properties of the LGE areas were assessed using the LGE heterogeneity, and the density was assessed by the entropy (LGE-entropy) and volume ratio of the enhancement voxel (LGE-volume ratio), respectively. Results NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7 and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments, p = 0.001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Of 5 patients with AF recurrence, NPAs outside the PV antrum were not ablated in 3 patients and the remaining NPAs were ablated, but their LGE-entropy and LGE-volume ratio were low. Conclusion AF rotors are mostly distributed in relatively weak and much more heterogenous LGE areas. This article is protected by copyright. All rights reserved.

Background Inflammation, such as that associated with intermediate CD14++ CD16+ monocytes and atrial structural remodeling (SRM), may be important in the recurrence of atrial fibrillation (AF) after catheter ablation. However, the relationship between the intermediate CD14++ CD16+ monocytes, SRM, and AF recurrence is unclear. Methods Twenty-four patients with AF were enrolled. The proportion of intermediate monocytes (PIM) was assessed before ablation by flow cytometry. As a surrogate marker of SRM, the volume ratio (VR) of signal intensity greater than 1 standard deviation on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) was calculated. We investigated whether PIM correlated with SRM on LGE-MRI and determined the optimal cutoff value for predicting AF recurrence. Results Univariate analysis revealed positive correlations between PIM and BNP with SRM (PIM: r = .593, p = .002; BNP: r = .567, p = .004). Multivariable analysis revealed that PIM was independently associated with VR on LGE-MRI (β = .522; p = .033). The finding of an area under the receiver operating characteristic curve of 0.750 revealed that a VR ≥ 13.3% on LGE-MRI as the optimal cutoff value to predict AF recurrence with 80% sensitivity and 71% specificity, which was associated with PIM ≥ 10.0%. Conclusion Intermediate monocytes were significantly positively correlated with SRM. PIM ≥ 10% was associated with a VR ≥ 13.3% on LGE-MRI, which predicted AF recurrence after catheter ablation.

BACKGROUND: A computer simulation model has demonstrated that an atrial fibrillation (AF) driver can be attached to heterogeneous fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study was to investigate whether radiofrequency (RF) applications in the fragmented LGE area (FLA) could terminate AF or convert it to atrial tachycardia (AT) and improve the rhythm outcome. METHODS: A total of 31 consecutive persistent AF patients with FLAs were enrolled (FLA ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). A favorable response was defined as direct AF termination or AT conversion during RF applications at the FLA. The rhythm outcome was compared between the FLA ablation group and FLA burden-matched pulmonary vein isolation (PVI) group. RESULTS: Favorable responses were found in 15 (48%) of 31 patients in the FLA group (AF termination in 7, AT conversion in 8 patients), but not in the PVI group. AF recurrence at 12 months follow-up was significantly less in the FLA ablation group than in the PVI group (4 [13%] vs. 12 [39%] of 31 patients, log-rank p=0.023). In patients with a favorable response, AT recurred in 1 (7%) of 15 patients but AF did not. CONCLUSIONS: FLA ablation could terminate AF or convert it to AT in half of the patients. No AF recurrence was documented in patients with a favorable response. This article is protected by copyright. All rights reserved.

We carried out a statistical analysis of the propagation characteristics of Es and Medium-Scale Traveling Ionospheric Disturbances (MSTIDs) by combining data of HF Doppler (HFD) sounder and Total Electron Content (TEC) obtained from the GPS receivers of GEONET (GPS-TEC) for 4 years from 2014 to 2017. We made use of Es reflection data from the HFD receivers in Sugito, Saitama (36.0°N, 139.7°E), Fujisawa, Kanagawa (35.3°N, 139.5°E), and Sugadaira, Nagano (36.4°N, 138.3°E) in Japan. By using this triangle observation, we succeeded in deriving the horizontal speed and direction of the motion of Es. In addition, we estimated the phase velocity of MSTIDs observed in the simultaneously obtained maps of GPS-TEC with the same triangle observation procedure. The speeds of Es and MSTIDs were commonly less than 100 m/s in most cases and their propagation direction was predominantly southwestward. This result is consistent with the statistical characteristics of nighttime MSTIDs observed in the previous studies. More importantly, good correspondence between the propagation characteristics of the two phenomena at two different altitudes confirms that Es and MSTIDs move in tandem with each other, further suggesting that Es in the E region plays an important role in the generation and propagation of MSTIDs in the F region. Graphical Abstract

High-dose methylprednisolone pulse therapy is widely used in patients with severe COVID-19. This therapy is known to have sufficient clinical effectiveness, but the optimal administration method is not known. In this study, we assessed the deterioration of oxygenation after methylprednisolone pulse therapy in patients with COVID-19 according to disease severity (oxygen requirement) at initiation of therapy. Ninety-nine patients with COVID-19 who received methylprednisolone pulse therapy at Saitama Medical University Hospital in Japan between October 2020 and October 2021 were retrospectively reviewed. Clinical outcomes were compared according to the fraction of inspired oxygen as a measure of disease severity at initiation of methylprednisolone pulse therapy. Based on the FIO2 level at initiation of methylprednisolone pulse therapy, patients were classified into an early treatment group (FIO2 ≤ 0.39; n = 21), a middle treatment group (FIO2 0.40–0.69; n = 38), and a late treatment group (FIO2 ≥ 0.70; n = 40). The frequency of administration of mechanical ventilation and the days of oxygen therapy in the middle group were lower than in the other groups. The frequency of adverse events was also lower in the middle group. Both late and early methylprednisolone pulse therapy may lead to further deterioration of COVID-19 and an increase in adverse events.

Background: Several algorithms have been proposed for differentiating the right and left outflow tracts (RVOT/LVOT) arrhythmia origins from 12-lead electrocardiograms (ECGs); however, the procedure is complicated. A deep learning (DL) model, a form of artificial intelligence, can directly use ECGs and depict the importance of the leads and waveforms. This study aimed to create a visualized DL model that could classify arrhythmia origins more accurately.Methods and Results: This study enrolled 80 patients who underwent catheter ablation. A convolutional neural network-based model that could classify arrhythmia origins with 12-lead ECGs and visualize the leads that contributed to the diagnosis using a gradient-weighted class activation mapping method was developed. The average prediction results of the origins by the DL model were 89.4% (88.2–90.6) for accuracy and 95.2% (94.3–96.2) for recall, which were significantly better than when a conventional algorithm is used. The ratio of the contribution to the prediction differed between RVOT and LVOT origins. Although leads V1 to V3 and the limb leads had a focused balance in the LVOT group, the contribution ratio of leads aVR, aVL, and aVF was higher in the RVOT group.Conclusions: This study diagnosed the arrhythmia origins more accurately than the conventional algorithm, and clarified which part of the 12-lead waveforms contributed to the diagnosis. The visualized DL model was convincing and may play a role in understanding the pathogenesis of arrhythmias.

Introduction. Macrolides could be a potential alternative treatment for Treponema pallidum infections in patients; however, macrolide-resistant T. pallidum is spreading rapidly worldwide. Hypothesis/Gap Statement. There are presently no alternatives to serological tests for syphilis that can be used to evaluate therapeutic effects due to the fact that T. pallidum cannot be cultured in vitro. Aim. In this study, we constructed a method for rapidly identifying T. pallidum and confirming macrolide resistance by using loop-mediated isothermal amplification (LAMP) with peptide nucleic acids (PNAs). Methodology. A set of LAMP primers was designed to span nucleotide positions 2058 and 2059 in 23S rRNA. A PNA clamping probe was also designed to be complementary to the wild-type sequence (A2058/A2059) and positioned to interfere with both the annealing of the 3′ end of the backward inner primer and the concomitant extension. Prior to the LAMP assay, swab samples from suspected syphilitic lesions were boiled for DNA extraction. Results. The assay had an equivalent detection limit of 1.0×101 copies/reaction and showed specificity against 38 pathogens. In the presence of a 4 µM PNA probe, LAMP amplified up to 1.0×101 copies/reaction using plasmids harbouring the complementary mutant sequences (A2058G or A2059G), whereas amplification was completely blocked for the wild-type sequence up to a concentration of 1.0×103 copies/reaction. For the 66 PCR-positive clinical specimens, the overall detection rate via LAMP was 93.9 % (62/66). Amplification was successful for all 53 mutant samples and was incomplete for all nine WT samples by the PNA-mediated LAMP assays. Conclusion. We developed a PNA-mediated LAMP method that enabled us to rapidly identify T. pallidum and determine its macrolide susceptibility via a culture-independent protocol.

With the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), a high-speed and convenient detection technology should be at the forefront of medical care worldwide. This study evaluated the usefulness of GeneSoC, a compact, high-speed reciprocal flow quantitative reverse transcription polymerase chain reaction system, for the detection of SARS-CoV-2. The results support the use of this system for the rapid identification of SARS-CoV-2. This approach can contribute to the strategic selection of initial management strategies for patients with COVID-19.

The $$\gamma$$ -Ray Evaluation with Iodoamphetamine for Cerebral blood flow Assessment (REICA) method is a new method for cerebral blood flow (CBF) quantification with SPECT and [123I] IMP, which does not require invasive arterial blood sampling, or the use of a regression formula. Moreover, it takes into consideration tracer retention, while the Graph-Plot (GP) method does not. This study aims to confirm the reliability of the REICA method in calculating CBF by accounting for pulmonary tracer retention artefact. Data of 100 patients were retrospectively analyzed. Washout rate (WR) was defined as 1- (max count /min count) in the lungs. The bias due to WR was analyzed by dividing the data into high/low WR groups and a multiple regression analysis was also performed. The REICA method did not show significant bias according to the $$\chi ^2$$ test ( $$p=0.07$$ ), while the GP method showed significant bias ( $$p=0.0006$$ ). Both the REICA and GP methods showed significant correlation with autoradiography (ARG) method ( $$p

We introduce a network observation of anomalous long-distance propagation of aeronautical navigation (NAV) very high-frequency (VHF) radio waves due to sporadic E layer (Es). The system has been operative since May 2019 at 6 stations in Japan. The receiver consists of a log-periodic antenna, air-band filter, software-defined radio and small computer which is capable of recording the strength of radio signals in the frequency band from 98 to 118 MHz with a temporal resolution of 2 s. The receiver covers not only the NAV band including VHF omnidirectional radio range (VOR), instrument landing system localizer (ILS LOC) and ground-based augmentation system VHF data broadcast (GBAS VDB) from 108 to 118 MHz, but also broadcasting channels from 98 to 108 MHz. Soon after the start of the full operation of the network observation, a strong Es event was detected by an ionosonde in Tokyo during the daytime on July 4, 2019, in which foEs (critical frequency of Es) was sometimes higher than 15 MHz. The VHF radio wave monitoring system detected multiple signatures of Es anomalous propagation (EsAP) at all the stations extending from Okinawa to Hokkaido. At some stations, the EsAP signatures continued for a few hours with some brief intervals of disappearance. The observed correspondence between the enhancement of foEs and the occurrence of anomalous propagation confirmed that an extreme electron density enhancement within Es caused the anomalous long-distance propagation of VHF NAV signals. The data from this network observation can be browsed at http://gwave.cei.uec.ac.jp/cgi-bin/vor/vhf.cgi in near real-time basis. This near real-time monitoring capability allows people in the aeronautical operation community such as air navigation service providers, pilots, and airline engineers to check the propagation environment of VHF NAV signals online, which contributes to a mitigation of ionospheric space weather impacts on the aeronautical navigation systems. Not only that the current method for detecting Es in a wide area can be used to visualize the spatial distribution of Es in two-dimensional fashion through a combination of other observation techniques such as ionosondes and total electron content (TEC) measurements using Global Navigation Satellite System (GNSS) signals.

Inflammation has been suggested to play a key role in the pathogenesis of atrial fibrillation (AF). Our hypothesis was that this inflammation, mediated by intermediate monocytes and toll-like receptor 4 (TLR4), causes the formation and expansion of low-voltage zones (LVZs). Prior to ablation, the monocyte subsets of 78 AF patients and TLR4 expression of 66 AF patients were analyzed via a flow cytometric analysis. Based on the CD14/CD16 expression, the monocytes were divided into three subsets: classical, intermediate, and non-classical. At the beginning of the ablation session, voltage mapping was performed. LVZs were defined as all bipolar electrogram amplitudes of

This case report concerns an 81-year-old woman with previously well-controlled hypertrophic obstructive cardiomyopathy (HOCM). She was referred to our hospital because of the acute onset of takotsubo syndrome. Echocardiography revealed basal hyperkinesis due to takotsubo syndrome superimposed on septal hypertrophy, which resulted in the reappearance of prominent left ventricular outflow tract obstruction (LVOTO). Although she developed cardiogenic shock triggered by atrial fibrillation, LVOTO was successfully mitigated by aggressive fluid resuscitation, rhythm control, and the administration of β-blocker. We herein report a rare case with catastrophic hemodynamics due to the incidental combination of HOCM and takotsubo syndrome.

Streptococcus pyogenes is a rare pathogen that causes endogenous endophthalmitis (EE). A healthy 58-year-old woman was diagnosed with EE secondary to septic arthritis caused by S. pyogenes. She underwent enucleation after hospitalization for 14 days with appropriate antibiotic cover. A literature search for outcomes of this condition revealed reports on only 10 eyes among 8 cases identified: 8 eyes (80%) developed poor visual outcome and 5 eyes (50%) underwent enucleation. There were no cases with immunocompromise. Our case report and literature review suggest the importance of awareness of the occurrence of S. pyogenes infection in immunocompetent hosts, and thus early diagnosis and aggressive treatment may be required to improve visual outcome.

A 75-year-old man was showed wall thickening just below esophagogastric junction(EGJ)by gastroscopy(GS). Biopsy indicated mucinous carcinoma. He was referred to our hospital. Computed tomography(CT), PET-CT showed EGJ cancer and splenic tumor. EGJ cancer was diagnosed GE, Siewert Type Ⅱ, GrePostAnt, Type 1, cT2, cN0, cM0, cStage Ⅰ. The patient underwent total gastrectomy, lower esophagectomy, D2+ #19, 20, 110, 111, 112 lymph nodes dissection, Rou-en- Y reconstruction, distal pancreatectomy, splenectomy, cholecystectomy, and enterostomy. Postoperative complication was pancreatic fistula(Grade Ⅱ). Pathological diagnosis was esophagogastric junction cancer, neuroendocrine carcinoma(NEC), GE, Siewert Type Ⅱ, GrePostAnt, Type 1, pT2(MP), pN1, pM0, pStage ⅡA. Splenic tumor was diagnosed splenic malignant lymphoma, large B-cell, diffuse(DLBCL), NOS, low-immediate risk. Patient was discharged 15 days after the operation and underwent adjuvant chemotherapy with S-1. In this case, he started taking S-1 because the prognosis of NEC is poorer than PSML. There was no evidence of recurrence after 5 months from gastrectomy. As a result of searching for"neuroendocrine tumor"and"malignant lymphoma"in the JAMAS, there was no report of NEC associated with malignant lymphoma. We experienced the rare case of primary splenic malignant lymphoma associated with EGJ NEC. In the case of gastric cancer with splenic tumor, malignant lymphoma of spleen should be concerned.

Many clinical studies have identified significant predictors or risk factors for the severity or mortality of coronavirus disease 2019 (COVID-19) cases. However, there are very limited reports on the risk factors for requiring oxygen therapy during hospitalization. In particular, we sought to investigate whether plasma glucose and HbA1c levels could be risk factors for oxygen therapy requirement.A single-center, retrospective study was conducted of 131 COVID-19 patients hospitalized at Saitama Medical University Hospital between March 2020 and November 2020. To identify the risk factors for oxygen therapy requirement during hospitalization, a stepwise multivariate binary logistic regression analysis was performed using several clinical parameters commonly obtained on admission, including plasma glucose and HbA1c levels.Of the 131 patients with COVID-19, 33.6% (44/131) received oxygen therapy during hospitalization. According to the logistic regression analysis, male sex (odds ratio [OR]: 8.76, 95% confidence interval [CI]: 1.65-46.5, P 0.05), age (OR: 1.07, 95% CI: 1.02-1.12, P 0.01), HbA1c levels (OR: 1.94, 95% CI: 1.09-3.44, P 0.05), and serum C-reactive protein (CRP) levels (OR: 2.22, 95% CI: 1.54-3.20, P 0.01) emerged as independent variables associated with oxygen therapy requirement during hospitalization.In addition to male sex, age, and serum CRP levels, HbA1c levels on admission may serve as a risk factor for oxygen therapy requirement during the clinical course of COVID-19, irrespective of diabetes history and status. This may contribute to the efficient delegation of limited numbers of hospital beds to patients at risk for oxygen therapy requirement.

Introduction: It has been reported that ventricular tachycardia (VT) non-inducibility at the end of ablation is associated with less likely VT recurrence. However, it is not clear whether we should use VT non-inducibility as routine end point in VT ablation. The aim of this study was to evaluate VT recurrence in patients in whom VT non-inducibility could not be achieved at the end of the RF ablation and the factors attributing to the VT recurrence. METHODS and RESULTS: We analyzed 84 consecutive patients that underwent RF ablation, and 64 patients in whom VT non-inducibility could not be achieved were studied. The primary endpoint was recurrence of any sustained VT during the follow-up. During a median follow-up period of 1.4 years (IQR:0.3-2.0), 22 (34%) of the cases had VT recurrences. In the multivariate analysis showed that an LVEF≥35% (HR:0.21; 95% CI:0.07- 0.54; P

Purpose We aimed to explore the velocity waveform characteristics of the retinal artery associated with age and the cardio-ankle vascular index (CAVI) as a conventional arterial stiffness marker by applying the Doppler optical coherence tomography (DOCT) flowmeter. Methods In this cross-sectional study, DOCT flowmeter imaging was performed in 66 participants aged 21 to 83 years (17 men, 49 women) with no history of eye diseases and no systemic diseases, except for hypertension. Retinal blood velocity waveform was analyzed where several parameters in time (upstroke time, T1, T2, T3, and T4) and area under the waveform (area elevation, area declination, A1, A2, A3, and A4) were extracted. Systolic blood pressure-adjusted Pearson's coefficients were calculated to determine the correlations of each parameter with age or CAVI. Results Corrected upstroke time (UTc) was the waveform parameter most positively correlated with age (r = 0.497, P < 0.001). Area declination was the waveform parameter most negatively correlated with age (r = -0.682, P < 0.001) and CAVI (r = -0.601, P < 0.001). Conclusions We extracted the waveform parameters associated with the risks of arterial stiffening. The velocity waveform analysis of the retinal artery with DOCT flowmeter potentially could become a new method for arterial stiffness identification. Translational Relevance DOCT flowmeter could evaluate arterial stiffening in a different way from the conventional method of measuring arterial stiffening using pressure waveform. Because the DOCT flowmeter can easily, quickly, and noninvasively provide a retinal blood velocity waveform, this system could be useful as a routine medical examination for arterial stiffening.

Background: Some of atrial fibrillation (AF) drivers are found in normal/mild late-gadolinium enhancement (LGE) areas, as well as moderate ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. Objective: The purpose of this study was to evaluate the impact of the AWT in normal/mild LGE areas on AF drivers. Methods: A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping), mild LGE areas were defined as areas with a volume ratio of the enhancement voxel of 0% to

Background A successful Radiofrequency (RF) ablation of ventricular tachycardia (VT) can prevent VT recurrence. It has been reported that VT non-inducibility at the end of RF ablation is associated with less likely VT recurrence in ischemic cardiomyopathy (ICM) and non-ICM (NCIM). However, it is not clear whether we should use VT non-inducibility as routine end point in RF ablation of VT. Purpose The aim of this study was to evaluate VT recurrence in patients who couldn't be achieved VT non-inducibility at the end of RF ablation and the factors attributed to VT recurrence in ICM and NICM patients. Methods Between January 2009 and April 2020, 84 consecutive patients (ICM: 34, NICM: 50) underwent RF ablation for drug-resistant VT in our hospital. VT non-inducibility was defined as any ventricular tachy-arrhythmia, including clinical VT, non-clinical VT, and VF, was not induced by programed stimuli at the end of session. Non-inducibility was achieved in 37 patients but it was not achieved in 47 patients (ICM: 18, NICM: 29). To evaluate the validity of “non-inducibility” as an end point of VT ablation, 47 patients (male: 40, mean age: 66±15 years) in whom non-inducibility of any ventricular tachyarrhythmia was not achieved were studied. The primary endpoint was recurrence of any sustained VT and VF during follow up period (mean follow-up period was 1.4 (range, 0.0, 2.0) years.) Results Mean left ventricular ejection fraction (LVEF) was 36±13%. Epicardial ablation was required in 8 patients. 32 patients had electrical storm at the time of ablation. Among them, 21 patients had VT recurrence and 26 patients had non-VT recurrence during follow-up period. VT recurrence rate was significantly lower in patients with LVEF≥35% than those with LVEF Conclusions Even if non-inducibility of any ventricular tachyarrhythmia wasn't achieved at the end of ablation, the patients with LVEF≥35% or who had ablated of VT isthmus might prevent VT recurrence. The validity of non-inducibility of any ventricular tachyarrhythmia should be evaluated in each patient's background. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Abbott, Medtronic

In Neisseria gonorrhoeae, fluoroquinolone resistance is caused by mutations on various genes, especially on gyrA. Locked nucleic acid DNA sequence was added to the forward primer for gyrA and subjected to real-time quantitative polymerase chain reaction, enabling simultaneous detection of N. gonorrhoeae and mutations associated with antimicrobial resistance.

The purpose of this study was to evaluate the diagnostic performance of retinal blood flow (RBF) measured with the Doppler optical coherence tomography (OCT) segmental scanning method to distinguish between healthy and glaucoma eyes.Fifty-eight patients with normal tension glaucoma (NTG) who had a single-hemifield visual field defect and 44 age-matched healthy subjects were enrolled. Retinal nerve fiber layer thickness (RNFLT) was measured with swept-source OCT. Superior and inferior temporal arteries (TAs) and temporal veins (TVs) RBF were measured with Doppler OCT. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to compare the diagnostic performances in the damaged and normal hemispheres.Multivariate regression analysis showed TA RBF and TV RBF were significantly reduced in the damaged and normal hemispheres. The ROC analysis showed that the AUC for quadrant RNFLT, TA RBF, and TV RBF were 0.973, 0.909, and 0.872 in the damaged hemisphere, respectively. The AUC values in the normal hemisphere were 0.783, 0.744, and 0.697, respectively. The combination of quadrant RNFLT and TA/TV RBF had a greater AUC than quadrant RNFLT alone in both damaged (AUC = 0.987) and normal (AUC = 0.825) hemispheres.In NTG eyes with single-hemifield damage, the RBF was found to be significantly reduced in the damaged and normal hemispheres independent from structural changes. The combination of RNFLT and RBF could improve diagnostic performances for glaucoma.Combining morphological and blood flow measurements with Doppler OCT may be useful in glaucoma diagnosis.