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Atrial switch procedures such as the Mustard operation were previously popular for the complete transposition of the great arteries (i.e. dextro-transposition of the great arteries [d-TGA]). Patients with d-TGA who underwent atrial switch procedures approximately three decades ago have now entered adulthood. A female patient in her 30s with d-TGA had a paradoxical embolic stroke following the initiation of a low-dose oestrogen plus progesterone oral pill for dysmenorrhoea. She underwent Mustard surgery when she was 2 years old. Following a series of procedures including implantation of a permanent pacemaker that was required because of sinus node dysfunction, she had reached adulthood, was living by herself and working independently. One month after taking the low-dose oestrogen plus progesterone oral pill, venous thrombosis occurred in the left soleus and left peroneal veins; and she experienced an acute ischaemic stroke in the right middle cerebral artery area. Transoesophageal echocardiography revealed that the shunt was present only during the Valsalva manoeuvre. Based on the examinations, the patient was diagnosed with juvenile ischaemic stroke as a result of a paradoxical embolism. These findings suggest that paradoxical cerebral embolism can occur as a late complication in patients with d-TGA who underwent the Mustard operation as children.

Pedagogical content knowledge (PCK) is one form of teachers’ professional knowledge in subject teaching, and teachers’ rich PCK enables effective instruction and improves students’ academic performance. However, there has been limited research on the relationships of individual difference characteristics of teachers to PCK among in-service elementary school teachers. Therefore, in addition to the demographic variables (gender and years of teaching experience) and psychological variables (beliefs about teaching and learning and teacher efficacy) examined in previous studies, this study attempted to clarify whether motivation for teaching is related to PCK. We conducted a web survey of in-service elementary school teachers in Japan (n = 267). The results showed that the traditional beliefs that students are to be controlled by their teachers and indifference, which describes a state of lack of motivation to prepare for class, were negatively associated with two elements of mathematical PCK (knowledge of learners and knowledge of instruction). Furthermore, multiple regression analysis revealed that traditional beliefs about teaching and learning were negatively associated with the knowledge of learners and indifference to subject instruction with knowledge of instruction. This suggests that teachers’ motivation for teaching is related to PCK, in addition to the variables that have been previously examined.

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently show physical dysfunction due to loss of muscle mass. This study aimed to clarify the reliability and validity of ultrasound in evaluating muscle mass and to analyze the patterns of change in muscle mass before and after allo-HSCT. We conducted a prospective observational study using data from 68 patients who had undergone their first allo-HSCT. We evaluated the thickness of the quadriceps, biceps, and suprahyoid muscle. Three individual evaluators underwent this examination for each muscle before transplantation and on days 30, 90, and 180 after allo-HSCT. Inter-rater reliability was calculated using the interclass correlation (ICC), and the level of correlation between muscle mass measured by ultrasound and psoas muscle mass assessed using computed tomography (CT) was assessed using Pearson correlation. ICC values ranged from 0.897 to 0.977 in the measurement. The correlation scores were 0.730, 0.546 and 0.579 between psoas muscle and the biceps, quadriceps, and suprahyoid muscle. The thickness of the biceps and quadriceps muscle were both significantly decreased after allo-HSCT from baseline. These results showed that the ultrasound technique was a reliable tool for evaluating muscle mass and detecting changes in muscle mass following allo-HSCT.

Background The longitudinal relationship between cancer-related fatigue (CRF) and physical function remains unclear. This study evaluated the association between pre-treatment physical functions and CRF exacerbation following concurrent chemoradiotherapy (CCRT). Methods The study included 42 cancer patients undergoing CCRT. Poor physical function was de ned as the presence of either or both low grip strength (3 points. A multivariate logistic regression analysis was performed to identify the association between poor physical function and exacerbation of CRF. Results Seventeen (40.5%) patients developed CRF exacerbation following CCRT. More patients had poor physical function in the CRF exacerbation group (58.8% vs. 20.0%; p=0.02). Poor physical function was an independent risk factor for exacerbation of CRF following CCRT after adjusting for confounders. Conclusions Poor physical function was a risk factor for exacerbation of CRF following CCRT. Assessing physical function may be useful in determining patients at high risk for CRF exacerbation following CCRT.

We examined the relationship between pedagogical content knowledge (PCK) test scores and elementary school teachers’ psychological variables, conceptions of teaching and learning and test utilization strategy, for mathematics. Through a web-based survey, participants responded to a six-item descriptive PCK test and to inventories of conceptions of teaching and learning and test utilization strategy. Data from 297 elementary school teachers were analyzed for associations with PCK scores. The results showed that constructivist conceptions and test utilization strategy were positively correlated with PCK test scores, and traditional conceptions were negatively correlated. In addition, the results of multiple regression analysis showed that traditional conception and test utilization strategy each showed unique associations with the PCK test. These results suggest the importance of teachers’ beliefs and test utilization strategies as related variables of teachers’ PCK.

Many previous studies related to self-regulated learning have demonstrated that students with higher academic achievement tend to use varied and effective learning strategies. However, they cannot acquire these strategies in a short period. If learning strategies are acquired and used gradually, it may help specify individual levels of use and teach its usage in a reasonable order. Therefore, this study analyzed data on strategy use with item response theory (IRT) to specify students’ level of strategy acquisition and determine how they are ordered. Questionnaire data on the frequency of learning strategy use were obtained from students in five universities (N = 472) and analyzed using the IRT model. It was shown that the average levels of students’ strategy acquisition were related to their universities’ academic achievement rankings.

Naringenin (NRG) is a plant-derived flavonoid. Due to its antioxidant, anti-inflammatory, and analgesic activities it is beneficial to human health and is often used as a functional food ingredient; however, it has poor water solubility and low in vivo bioavailability. Therefore, the efficacy of NRG can be improved by enhancing its water solubility to increase gastrointestinal absorption. Conventional methods for the formulation of NRG are very complex and use toxic organic solvents, making them impractical for the production of functional foods. The objective of this study was to develop a safe and effective NRG-based functional food material. Previously, we established a technology to prepare amorphous solid dispersions (SDs) from functional food ingredients with poor water solubility and used hot-melt extrusion technology that is comparatively simple and does not involve the use of organic solvents. In this study, we prepared NRG SD and evaluated them both physicochemically and biochemically. NRG SD had superior water solubility and gastrointestinal absorption relative to native NRG and showed higher analgesic efficacy in rats than crystalline NRG. NRG SD was administered to mice in a mixed diet for 28 days, and organ weights and hematological/clinical biochemical parameters were assessed. NRG SD did not demonstrate severe adverse effects. The results suggest that NRG SD is a safe and highly efficacious formulation that can be used as a functional food material in the future.

Although a significant association between periodontal disease and atherosclerotic cardiovascular disease has been reported, their cause-to-effect relationship remains controversial. This randomized controlled clinical trial aimed to investigate the effect of advanced self-care on atherosclerotic cardiovascular disease-related vascular function markers flow-mediated brachial artery dilatation (FMD) and serum asymmetric dimethylarginine (ADMA) level in patients with early-stage periodontal disease. The study was designed as a parallel group, 3-month follow-up, open-label, randomized controlled trial. The control group received standard care for periodontal diseases, whereas the test group additionally applied disinfectant using a custom-fabricated prescription tray for advanced self-care twice a day. Overall, 110 patients provided data for FMD and serum ADMA level. No significant improvements in FMD were observed in the control (mean increase, -0.1%; 95% confidence interval [CI], -1.0-0.8; P = 0.805) or test (mean increase, -0.3%; 95% CI, -1.1-0.4; P = 0.398) group. No significant changes in serum ADMA levels were observed (mean reduction, 0.01 μmol/L; 95% CI, -0.00-0.02; P = 0.366 and mean reduction, 0.00 μmol/L; 95% CI, -0.01-0.01; P = 0.349, respectively). No significant between-group differences were found in FMD (mean difference, -0.2%; 95% CI, -1.4-0.9; p = 0.708) or serum ADMA levels (mean difference, 0.01 nmol/L; 95% CI, -0.00-0.03; p = 0.122). Significant improvements in the average probing pocket depth were observed in the control and test groups. The bleeding on probing score in the test group was significantly reduced, while that in the control group was reduced, although not significantly. Periodontal care for a 3-month duration did not provide better endothelial function although improvements of periodontal status in patients with early-stage periodontal diseases. This trial is registered in UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/; ID: UMIN000023395).

Background: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan’s demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication. Methods: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed. Results: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies. Conclusion: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.

PURPOSE:The lamina cribrosa (LC) is known to play a critical role in the pathogenesis of glaucoma. Although it has been reported that striae-shaped or slit-shaped lamina pores are more frequent in eyes with primary open angle glaucoma (POAG), this observation is based only on fundus photography. The primary object of this study is to perform layer-by-layer comparisons of the shape of lamina pores within the LC in vivo. DESIGN:Cross-sectional study. METHODS:Optic nerve head B-scans were obtained using custom-made broad-wavelength optical coherence tomography with a mode-locked laser. A total of 300 single B-scans per eye were obtained and three-dimensional images were rendered from these image sequences to obtain 2-μm thin-slice en face images of the LC. Elongation indices (EIs) of the lamina pores were measured from the anterior surface (AS) of the LC to the deeper layers in 40-μm increments. RESULTS:Thirteen eyes from 10 primary open angle glaucoma (POAG) patients of mean deviation -15.2 (-16.5, -12.9) (median [25,75 percentile]) dB and 10 eyes from 7 normal controls were studied. Although the EI value was not significantly different between the superior, temporal and inferior regions of the LC at any depth level in either group, it was greater at the AS than at the 40 μm and 80 μm depth levels (P < .001) in both groups, and was greater in the POAG group only at the AS and 40 μm depth level (P ≤ .05). After adjustment for age and refraction, the effects of depth and presence of POAG on the EI value remained significant. Also, the severity of glaucoma and depth were significant factors associated with EI in multivariate analysis. CONCLUSIONS:Elongation of lamina pores was significantly more evident at the anterior surface and the 40-μm depth level of the LC in POAG eyes than in normal eyes, suggesting that nerve fiber bundles passing through the LC were under greater stress in the anterior layers of the LC.

This paper reviews techniques for improving the temporal contrast and spatial beam quality in an ultra-intense laser system that is based on chirped-pulse amplification (CPA). We describe the design, performance, and characterization of our laser system, which has the potential for achieving a peak power of 600 TW. We also describe applications of the laser system in the relativistically dominant regime of laser-matter interactions and discuss a compact, high efficiency diode-pumped laser system.

The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major pathophysiological feature of patients with Parkinson's disease (PD). As nigral DA neurons contain both neuromelanin (NM) and dopamine transporter (DAT), decreased intensities in both NM-sensitive MRI and DAT PET reflect decreased DA neuronal density. This study demonstrates that a more specific metric for the nigral DA neuronal density can be derived with multimodal MRI and PET. Participants were 11 clinically diagnosed PD patients and 10 age and gender matched healthy controls (HCs). Two quantities, the NM-related index (RNM) and the binding potential of the radiotracer [18F]FE-PE2I to DAT (BPND) in SN, were measured for each subject using MRI and PET, respectively. Principal component analysis (PCA) was applied to the multimodal data set to estimate principal components. One of the components, PCP, corresponds to a basis vector oriented in a direction where both BPND and RNM increase. The ability of BPND, RNM and PCP to discriminate between HC and PD groups was compared. Correlation analyses between the motor score of the unified Parkinson's disease rating scale and each metric were also performed. PCP, BPND and RNM for PD patients were significantly lower than those for HCs (F = 16.26, P

To measure horizontal and vertical lamina cribrosa (LC) tilt angles and investigate associated factors using prototype optical coherence tomography (OCT) with a broad wavelength laser light source.Cross sectional study.Twenty-eight no glaucoma eyes (from 15 subjects) and 25 glaucoma eyes (from 14 patients) were enrolled. A total of 300 optic nerve head B-scans were obtained in 10 µm steps and the inner edge of Bruch's membrane opening (BMO) was identified as the reference plane. The vertical and horizontal angles between BMO line and approximate the best-fitting line for the surface of the LC were measured and potential associated factors were estimated with univariate and multivariate logistic regression analyses.The median (interquartile range) horizontal and vertical tilt angles were 7.10 (2.43-11.45) degrees and 4.15 (2.60-6.85) degrees in eyes without glaucoma and 8.50 (4.40-14.10) degrees and 9.30 (6.90-14.15) degrees in glaucoma eyes, respectively. The refractive errors had a statistically significant association with horizontal LC tilt angles (coefficients, -1.53 per diopter) and glaucoma had a significant correlation with vertical tilt angles (coefficients, 6.56) using multiple logistic regression analysis (p

A novel investigational antidepressant with high affinity for the serotonin transporter and the serotonin 1A (5-HT(1A)) receptor, called Wf-516 (structural formula: (2S)-1-[4-(3,4-dichlorophenyl)piperidin-1-yl]-3-[2-(5-methyl-1,3,4-oxadiazol-2-yl)benzo[b]furan-4-yloxy]propan-2-ol monohydrochloride), has been found to exert a rapid therapeutic effect, although the mechanistic basis for this potential advantage remains undetermined. We comparatively investigated the pharmacokinetics and pharmacodynamics of Wf-516 and pindolol by positron emission tomographic (PET) and autoradiographic assays of rat brains in order to elucidate their molecular interactions with presynaptic and postsynaptic 5-HT(1A) receptors. In contrast to the full receptor occupancy by pindolol in PET measurements, the binding of Wf-516 to 5-HT(1A) receptors displayed limited capacity, with relatively high receptor occupancy being achieved in regions predominantly containing presynaptic receptors. This selectivity was further proven by PET scans of neurotoxicant-treated rats deficient in presynaptic 5-HT(1A) receptors. In addition, [(35)S]guanosine 5'-O-[γ-thio]triphosphate autoradiography indicated a partial agonistic ability of Wf-516 for 5-HT(1A) receptors. This finding has lent support to reports that diverse partial agonists for 5-HT(1A) receptors exert high sensitivity for presynaptic components. Thus, the present PET data suggest a relatively high capacity of presynaptic binding sites for partial agonists. Since our in vitro and ex vivo autoradiographies failed to illustrate these distinct features of Wf-516, in vivo PET imaging is considered to be, thus far, the sole method capable of pharmacokinetically demonstrating the unique actions of Wf-516 and similar new-generation antidepressants.

Dopamine D(2) receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2) receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11)C]raclopride and L-[β-(11)C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2) receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2) receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

The function of transplanted hepatocytes in acute ischemic liver failure was studied in an experimental model using rats. Ischemic liver failure was induced by occlusion of the proximal portal vein and hepatic artery immediately following extracorporeal portofemoral venous bypass. All rats were bred in a closed colony. Rats in Group 1 were untreated and served as controls (n = 10). Rats in Group 2 received an intrasplenic transplant of hepatocytes (1 × 107 cells) 48 h before liver ischemia (n = 10). Serum ammonia and blood glucose were measured before, and 1 h after, ischemia. Serum ammonia was significantly higher than normal (Group 1, 930 μg/dL vs < 110 μg/dL) after liver ischemia. On the other hand, serum ammonia in group 2 also was elevated (355 μg/dL), but significantly less so than in Group 1 (p < 0.001). Blood glucose was lower in both groups after liver ischemia, compared to normal (50-100 mg/dL), but it was higher in Group 2 (30 mg/dL) than in Group 1 (14 mg/dL, p < 0.01). Liver histology 1 h after ischemia showed similar degrees of necrosis in the two groups. Transplanted hepatocytes were viable, and clearly identified in the splenic parenchyma after ischemia. Intrasplenic transplanted hepatocytes provide temporary metabolic support of acute ischemic liver failure in rats, as reflected by enhanced ammonia removal and gluconeogenesis.