Improving image quality using the pause function combination to PROPELLER sequence in brain MRI: a phantom study.

While some MRI systems offer a "pause" function, combining it with the PROPELLER method for image quality improvement remains underexplored. This study investigated whether repositioning the head after pausing during PROPELLER imaging enhances image quality. All brain phantom images in this study were obtained using a 3.0 T MRI and acquired using the fast spin-echo T2WI-based PROPELLER with motion correction. By combining the angle of rotational motion of the head phantom and the number of repositioning after a pause, two studies including seven trials were performed. Increasing the rotation angle decreased the image quality; however, pausing the image and repositioning the head phantom to the original angle improved the image quality. A similar result was obtained by repositioning the angle closer to its original angle. Experiments with multiple head movements showed that pausing the scan and repositioning the phantom with each movement improved image quality.

Radical Nitrososulfonation of Propargyl Alcohols: Thiazolidine-2,4-dione-Assisted Synthesis of 5-Alykyl-4-sulfonylisoxazoles.

In this study, we discover a good NO/HNO precursor, N-hydroxypyridinesulfonamide, and the regioselective radical nitrososulfonylation reaction of propargyl alcohols. Direct and unique isoxazole synthesis afforded a good-to-high yield of 5-alkyl-3-aryl-4-pyridinesulfonylisoxazoles. Copper-catalyzed aerobic oxidation could efficiently proceed in the presence of thiazolidine-2,4-dione. This work provides a powerful method for the synthesis and functionalization of alkyl-substituted isoxazoles and explores a new investigation route for drug-drug discovery.

Modified procedures of subcutaneous implantable cardioverter defibrillator implantation for a child with small body size.

Modified procedures of subcutaneous implantable cardioverter defibrillator (S-ICD) implantation for a child with a small body size are presented. This report demonstrates the feasibility of novel diagonal S-ICD lead implantation method.

Case report: high-dose carvedilol as a potential key drug for arrhythmias in histiocytoid cardiomyopathy.

Background: Histiocytoid cardiomyopathy is a rare infancy cardiac disorder manifesting as severe cardiac arrhythmias or dilated cardiomyopathy. There is no specific treatment for these arrhythmias. This is the first report of infantile histiocytoid cardiomyopathy whose refractory ventricular arrhythmias were successfully controlled by high-dose carvedilol. Case summary: A 4-month-old girl presented with asystole, and recurrent ventricular tachycardias. From the histological findings and clinical symptoms, she was diagnosed as histiocytoid cardiomyopathy. Sedatives were the most effective therapy for her arrhythmia, but the cardiac sympathetic denervation was not effective enough. Finally, her ventricular arrhythmias were controlled with high-dose carvedilol, and she was discharged on hospitalization Day 393. Discussion: Carvedilol is the only beta blocker that directly acts on the ryanodine receptor (RyR2) and inhibits store-overload-induced Ca2+ release (SOICR) in myocardium at high dosage. The arrhythmias did not disappear with bisoprolol, landiolol, or verapamil, but high-dose carvedilol was effective. This clinical course suggested that the arrhythmias in histiocytoid cardiomyopathy might be related with SOICR. High-dose carvedilol might be a key drug for patients with histiocytoid cardiomyopathy.

Interneurons of fan-shaped body promote arousal in Drosophila.

Sleep is required to maintain physiological functions and is widely conserved across species. To understand the sleep-regulatory mechanisms, sleep-regulating genes and neuronal circuits are studied in various animal species. In the sleep-regulatory neuronal circuits in Drosophila melanogaster, the dorsal fan-shaped body (dFB) is a major sleep-promoting region. However, other sleep-regulating neuronal circuits were not well identified. We recently found that arousal-promoting T1 dopamine neurons, interneurons of protocerebral bridge (PB) neurons, and PB neurons innervating the ventral part of the FB form a sleep-regulatory circuit, which we named "the PB-FB pathway". In the exploration of other sleep-regulatory circuits, we found that activation of FB interneurons, also known as pontine neurons, promoted arousal. We then found that FB interneurons had possible connections with the PB-FB pathway and dFB neurons. Ca2+ imaging revealed that FB interneurons received excitatory signals from the PB-FB pathway. We also demonstrated the possible role of FB interneurons to regulate dFB neurons. These results suggested the role of FB interneurons in sleep regulation.

Thirty-year outcome in children with hypertrophic cardiomyopathy based on the type.

BACKGROUND: We reviewed the long-term outcome of children with hypertrophic cardiomyopathy (HCM) based on the type. METHODS: We reviewed the medical records of 100 patients (male 54 female 46) with HCM at our hospital between 1977 and 2015. The survival and cardiac event-free survival rates were calculated by the Kaplan-Meier method. RESULTS: The age at the time of the diagnosis ranged from 0 to 15 years with a median of 8 years. The number of patients with Noonan syndrome and hypertrophic obstructive cardiomyopathy (HOCM), idiopathic HCM (i-HCM), and secondary HCM (s-HCM) was 13, 13, 65, and 9 respectively. A dilated phase of HCM occurred in 24 patients. Nineteen (79 %) of the 24 patients died of heart failure, and two underwent a heart transplantation. Eight (33 %) of the 24 patients had s-HCM. The median age when a dilated phase occurred was 15 years old, and the median interval from the initial diagnosis to the dilated phase was 8 years. The median time from the diagnosis of a dilated phase to death was 1.6 years. Sudden death and implantable cardioverter defibrillator implantations occurred in 6 and 11 patients at around 15 years old, respectively. The 20-year survival rates were as follows: Noonan syndrome 84 %; HOCM 82 %; i-HCM 71 %; and s-HCM 17 %. Overall, the survival rates at 10, 20, and 30 years were 83 % (95 % confidence interval 73-89), 69 % (58-78), and 63 % (50-74), respectively. The overall cardiac event-free survival rates at 10, 20, and 30 years were 57 % (47-67), 39 % (31-50), and 32 % (21-44), respectively. CONCLUSION: The long-term outcome in children with HCM was poor, and the outcome of s-HCM was very poor. The occurrence of a dilated phase worsened the outcome in HCM patients. Sudden death and d-HCM often occurred at around 15 years old.

A machine learning model that emulates experts' decision making in vancomycin initial dose planning.

Vancomycin is a glycopeptide antibiotic that is a primary treatment for methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness and prevent nephrotoxicity, therapeutic drug monitoring (TDM) of trough concentrations is recommended. Initial vancomycin dosing regimens are determined based on patient characteristics such as age, body weight, and renal function, and dosing strategies to achieve therapeutic concentration windows at initial TDM have been extensively studied. Although numerous dosing nomograms for specific populations have been developed, no comprehensive strategy exists for individually tailoring initial dosing regimens; therefore, decision making regarding initial dosing largely depends on each clinician's experience and expertise. In this study, we applied a machine-learning (ML) approach to integrate clinician knowledge into a predictive model for initial vancomycin dosing. A dataset of vancomycin initial dose plans defined by pharmacists experienced in vancomycin TDM (i.e., experts) was used to build the ML model. Although small training sets were used, we established a predictive model with a target attainment rate comparable to those of experts, another ML model, and commonly used vancomycin dosing software. Our strategy will help develop an expert-like predictive model that aids in decision making for initial vancomycin dosing, particularly in settings where dose planning consultations are unavailable.

Impact of cascade screening for catecholaminergic polymorphic ventricular tachycardia type 1.

OBJECTIVE: Human cardiac ryanodine receptor 2 (RYR2) shows autosomal-dominant inheritance in catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1); however, de novo variants have been observed in sporadic cases. Here, we investigated CPVT1-related RYR2 variant inheritance and its clinical significance between familial and de novo cases. METHODS: We enrolled 82 independent CPVT1 probands (median age: 10.0 (7.0-13.0) years; 45 male) carrying the RYR2 variants and whose biological origin could be confirmed by parental genetic analysis: assured familial inheritance (familial group: n=24) and de novo variants (de novo group: n=58). We examined the clinical characteristics of the probands and their family members carrying the RYR2 variants. RESULTS: In the de novo group, the RYR2 variants were more likely located in the C-terminus domain and less likely in the N-terminus domain than those in the familial group. The cumulative incidence of the first cardiac events (syncope and cardiac arrest (CA) or CA only) of the probands at the age of 5 and 10 years was higher in the de novo group than in the familial group. Nearly half of the probands in both groups experienced CA events before diagnosis. Only 37.5% of their genotype-positive parents had symptoms; however, at least 66.7% of the genotype-positive siblings were symptomatic. CONCLUSIONS: CPVT1 probands harbouring de novo RYR2 variants showed an earlier onset of symptoms than those with assured familial inheritance. Cascade screening may enable early diagnosis, risk stratification and prophylactic therapeutic intervention to prevent sudden cardiac death of probands and potential genotype-positive family members.

Coronary artery aneurysms of unknown origin in a 14-year-old girl.

The case of a 14-year-old girl with acute myocardial infarction due to coronary artery aneurysms (CAAs) of unknown origin, which resembled coronary artery lesions caused by Kawasaki disease, is reported. She was transferred to our hospital due to chest pain with ST-T elevation. She had no history of Kawasaki disease. On the first admission, she was misdiagnosed with acute myocarditis. Then, 54 days later, she experienced chest pain with exertional dyspnea. Her electrocardiogram showed negative T waves in the chest leads. A CAA of the left coronary artery was suspected on two-dimensional echocardiography. Coronary angiograms showed 90% stenosis and multiple CAAs of the left anterior descending artery and the bifurcation of the left coronary artery. Both the right coronary artery and left circumflex artery were occluded. A left ventriculogram showed dyskinesis and an aneurysm at the apex. She underwent triple-vessel coronary artery bypass grafting, and her symptoms improved. In addition, an intracranial aneurysm was also found on cerebral angiography. There were no specific laboratory findings other than SS-A antibodies. It was suspected that the weakness of the vessels was related to the disease. It may have been a different disease that was never previously detected, but her CAAs were Kawasaki-like CAAs.

Aging-related metabolic changes in the extensor digitorum longus muscle of senescence-accelerated mouse-prone 8.

AIM: Sarcopenia - aging-related loss of muscle mass and muscle strength - is a key feature of the frailty model. In the present study, we aimed to elucidate the molecular biological changes associated with aging in the extensor digitorum longus muscle of senescence-accelerated mouse prone 8 mouse model by capillary electrophoresis-mass spectrometry. METHODS: Three groups of senescence-accelerated mouse prone 8 mice were used, namely, 12-week-old (young; n = 5), 40-week-old (elderly; n = 5) and 55-week-old mice (late elderly; n = 5). The extensor digitorum longus muscle was collected. After preliminary analyses, metabolome analysis was carried out by capillary electrophoresis-mass spectrometry. Additionally, we examined whether the activity of enzymes in the metabolic pathway fluctuated with aging, by real-time polymerase chain reaction. RESULTS: Among the 116 water-soluble metabolites associated with the central energy metabolism pathway, changes were observed in 19 metabolites between 12- and 40 -weeks-old, in 40 metabolites between 40- and 55-weeks-old, and in 57 metabolites between 12- and 55-weeks-old. The fluctuated metabolites that were common among the groups were Val, putrescine and His. The levels of putrescine, associated with cell proliferation, protein synthesis and nucleic acid synthesis, and ß-Ala and His, a component of carnosine that is characterized by its anti-oxidant and anti-fatigue effects, decreased with age. CONCLUSIONS: We confirmed that there were two aging-related metabolic changes in the extensor digitorum longus muscle of senescence-accelerated mouse prone 8 mice. Based on the changes in metabolites, cell senescence and fatigue in the extensor digitorum longus muscle might increase in old mice compared with those in young mice, showing molecular biological changes with aging. Geriatr Gerontol Int 2022; 22: 160-167.

Protocerebral Bridge Neurons That Regulate Sleep in Drosophila melanogaster.

The central complex is one of the major brain regions that control sleep in Drosophila. However, the circuitry details of sleep regulation have not been elucidated yet. Here, we show a novel sleep-regulating neuronal circuit in the protocerebral bridge (PB) of the central complex. Activation of the PB interneurons labeled by the R59E08-Gal4 and the PB columnar neurons with R52B10-Gal4 promoted sleep and wakefulness, respectively. A targeted GFP reconstitution across synaptic partners (t-GRASP) analysis demonstrated synaptic contact between these two groups of sleep-regulating PB neurons. Furthermore, we found that activation of a pair of dopaminergic (DA) neurons projecting to the PB (T1 DA neurons) decreased sleep. The wake-promoting T1 DA neurons and the sleep-promoting PB interneurons formed close associations. Dopamine 2-like receptor (Dop2R) knockdown in the sleep-promoting PB interneurons increased sleep. These results indicated that the neuronal circuit in the PB, regulated by dopamine signaling, mediates sleep-wakefulness.

Electrocardiographic Diagnosis of Hypertrophic Cardiomyopathy in the Pre- and Post-Diagnostic Phases in Children and Adolescents.

BACKGROUND: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.Methods and Results:ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria. CONCLUSIONS: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

PZLAST: an ultra-fast amino acid sequence similarity search server against public metagenomes.

SUMMARY: : Similarity searches of amino acid sequences against the public metagenomic data can provide users insights about the function of sequences based on the environmental distribution of similar sequences. However, a considerable reduction in the amount of data or the accuracy of the result was necessary to conduct sequence similarity searches against public metagenomic data, because of the vast data size more than Terabytes. Here, we present an ultra-fast service for the highly accurate amino acid sequence similarity search, called PZLAST, which can search the user's amino acid sequences to several Terabytes of public metagenomic sequences in ∼10-20 min. PZLAST accomplishes its search speed by using PEZY-SC2, which is a Multiple Instruction Multiple Data many-core processor. Results of PZLAST are summarized by the ontology-based environmental distribution of similar sequences. PZLAST can be used to predict the function of sequences and mine for homologs of functionally important gene sequences. AVAILABILITY AND IMPLEMENTATION: PZLAST is freely accessible at https://pzlast.riken.jp/meta without requiring registration. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Abdominal aortic thrombus formation in a neonate with an interrupted aortic arch.

We note the risk of paradoxical embolism in patients with congenital heart defects with a right-to-left shunt. These patients should be managed to ensure that abdominal aortic thrombi are not overlooked when their clinical conditions change.

Na+/Ca2+ exchanger mediates cold Ca2+ signaling conserved for temperature-compensated circadian rhythms.

Circadian rhythms are based on biochemical oscillations generated by clock genes/proteins, which independently evolved in animals, fungi, plants, and cyanobacteria. Temperature compensation of the oscillation speed is a common feature of the circadian clocks, but the evolutionary-conserved mechanism has been unclear. Here, we show that Na+/Ca2+ exchanger (NCX) mediates cold-responsive Ca2+ signaling important for the temperature-compensated oscillation in mammalian cells. In response to temperature decrease, NCX elevates intracellular Ca2+, which activates Ca2+/calmodulin-dependent protein kinase II and accelerates transcriptional oscillations of clock genes. The cold-responsive Ca2+ signaling is conserved among mice, Drosophila, and Arabidopsis The mammalian cellular rhythms and Drosophila behavioral rhythms were severely attenuated by NCX inhibition, indicating essential roles of NCX in both temperature compensation and autonomous oscillation. NCX also contributes to the temperature-compensated transcriptional rhythms in cyanobacterial clock. Our results suggest that NCX-mediated Ca2+ signaling is a common mechanism underlying temperature-compensated circadian rhythms both in eukaryotes and prokaryotes.

Cky811 protein expressed by polydnavirus and venom gland of Cotesia kariyai regulates the host Mythimna separata larvae immune response function of C-type lectin responsible for foreign substance recognition which suppresses its melanization and encapsulation.

Cotesia kariyai (Ck) larvae implanted into the body cavity of the Mythimna separata (armyworm) larvae get melanized and encapsulated after adhesion by hemocytes called hyperspread cells (HSCs). The present study showed that HSCs could not adhere to the implanted Ck larvae in armyworm larvae after injection of Ck polydnavirus (CkPDV) + venom (V), thus melanization and encapsulation could not occur. A C-type lectin called Mys-IML of the host armyworm larvae was considered to be involved in the recognition of foreign substances which always expressed in hemocytes. The CkPDV DNA encodes a C-type lectin called Cky811 that has high amino acid homology to Mys-IML. HSCs did not adhere when CkPDV + V was mixed with the hemolymph of armyworm larvae on glass slides and incubated in vitro, but the addition of anti-Cky811 antibody enabled HSCs to adhere. The messenger RNA (mRNA) expression of Mys-IML in armyworm larvae injected with CkPDV + V became undetectable by 6 h. On the contrary, Cky811 mRNA was well expressed in the hemocytes of armyworm larvae injected with CkPDV + V from 0.5 to 6 h. Cky811 protein was also detected in the crude extracts from Ck venom gland + Ck venom reservoir, suggesting that these proteins regulate foreign substance recognition by the armyworm within 0.5 h. These results suggest that CkPDV + V suppresses mRNA expression of Mys-IML, and that Cky811 protein expressed in hemocytes regulates foreign substance recognition of Mys-IML, resulting in inhibition of the downstream reaction steps: HSCs adhesion, melanization, and encapsulation.

Simulating an ultra-broadband concept for Exawatt-class lasers.

The rapid development of the optical-cycle-level ultra-fast laser technologies may break through the bottleneck of the traditional ultra-intense laser [i.e., Petawatt (PW, 1015 W) laser currently] and enable the generation of even higher peak-power/intensity lasers. Herein, we simulate an ultra-broadband concept for the realization of an Exawatt-class (EW, 1018 W) high peak-power laser, where the wide-angle non-collinear optical parametric chirped-pulse amplification (WNOPCPA) is combined with the thin-plate post-compression. A frequency-chirped carrier-envelope-phase stable super-continuum laser is amplified to high-energy in WNOPCPA by pumping with two pump-beamlets and injected into the thin-plate post-compression to generate a sub-optical-cycle high-energy laser pulse. The numerical simulation shows this hybrid concept significantly enhances the gain bandwidth in the high-energy amplifier and the spectral broadening in the post-compression. By using this concept, a study of a prototype design of a 0.5 EW system is presented, and several key challenges are also examined.

Number of concomitant drugs with thrombocytopenic adverse effects and the extent inflammatory response resolution are risk factors for thrombocytopenia in patients treated with linezolid for more than 14 days.

Prolonged treatment with linezolid (LZD) is known to cause thrombocytopenia. However, some patients do not develop thrombocytopenia despite long-term administration of LZD. To determine the risk factors for LZD-associated thrombocytopenia in patients undergoing long-term LZD therapy, we conducted a retrospective cohort study among 212 patients receiving LZD treatment between December 2011 and June 2014 at a tertiary referral university hospital in Nagoya, Japan. Of the 217 patients who received LZD, 37 were treated with LZD for more than 14 days and were enrolled in the study. We compared data on demographic characteristics, underlying disease, microbiology, concomitant drugs, and laboratory tests between the thrombocytopenia group and the non-thrombocytopenia group. Thrombocytopenia was defined as having a platelet count < 100 × 103/µL or a ≥ 50% reduction in platelet count compared to baseline. Among the 37 patients who received LZD for more than 14 days, 17 (45.9%) developed thrombocytopenia. Multivariate logistic regression revealed that both the number of concomitant drugs with thrombocytopenic adverse effects (DTADE) (OR = 1.690; 95% CI = 1.037-2.754; P = 0.035) and a small decrease in the level of C-reactive protein (CRP) 14 days post-administration (OR = 0.965; 95% CI = 0.939-0.993; P = 0.013) were associated with thrombocytopenia during long-term LZD therapy. Therefore, the number of concomitant DTADE and a small decrease in CRP on the 14th day of treatment were key factors for the appearance of LZD-associated thrombocytopenia in patients with long-term LZD therapy. Our findings may be useful for preventing thrombocytopenia in patients treated with LZD for longer than 14 days.

Diffusion-weighted imaging with simultaneous multi-slice echo-planar technique for the diagnosis of breast magnetic resonance imaging.

PURPOSE: To evaluate the diagnostic potential of simultaneous multi-slice echo-planar diffusion-weighted imaging (DWI) (SMS-DWI). MATERIALS AND METHODS: A total of 55 consecutive patients underwent breast magnetic resonance imaging (MRI) between April and September 2018. SMS-DWI and single-shot echo-planar DWI (SS-EPI-DWI) sequences were obtained with the following parameters: b value, 0, 850, and 1200 mm2/s for both; spacing between sections, 2 mm for SMS-DWI and 3 mm for SS-EPI-DWI. Lesion visibility was assessed by two radiologists, and minimal and maximal apparent diffusion coefficients (ADCs) for masses were measured. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Of the 55 cases, 23 (41.8%) were malignant and 32 (58.2%) were benign. Visual conspicuity was superior on SMS-DWI in 47.1% (n = 16/34) or 55.9% (n = 19/34) among the lesions visible on DWI and ADC. ROC curve analyses revealed an area under the curve of 0.87 [95% confidence interval (CI) 0.68-1.00], 0.94 (95% CI 0.86-1.00), 0.93 (95% CI 0.84-1.00) and 0.90 (95% CI 0.77-1.00) for minimal and maximal ADC on SMS-DWI and ADC on SS-EPI-DWI, respectively. CONCLUSION: Simultaneous multi-slice technique provided breast DWI of better visual conspicuity and comparable diagnostic performance with shorter acquisition time.