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Diaphragmatic reconstruction is required for extensive diaphragmatic defects associated with tumor resection. Methods using artificial mesh and autologous tissues, such as pedicled flaps, have been reported predominantly for diaphragmatic reconstruction. We present the case of a 61-year-old woman who presented with a 14 × 13 × 12 cm tumor in the abdominal cavity of the upper left abdomen on computed tomography. The diaphragm defect measuring 12 × 7 cm that occurred during excision of the malignant tumor was reconstructed using the rectus abdominis muscle and fascial flap. The flap has vertical and horizontal vascular axes; therefore, blood flow is stable. It also has the advantage of increasing the range of motion and reducing twisting of the vascular pedicles. Fascial flap does not require processing such as thinning and can be used during suture fixation. This procedure, which has rarely been reported so far, has many advantages and may be a useful option for diaphragm reconstruction.

Copper and zinc are essential for normal brain functions. Both are localized in presynaptic vesicles and are secreted into synaptic clefts during neuronal excitation. Despite their significance, excesses of copper and zinc are neurotoxic. In particular, excess zinc after transient global ischemia plays a central role in the ischemia-induced neurodegeneration and pathogenesis of vascular type senile dementia. We previously found that sub-lethal concentrations of copper remarkably exacerbated zinc-induced neurotoxicity, and we investigated the molecular pathways of copper-enhanced zinc-induced neurotoxicity. The endoplasmic reticulum stress pathway, the stress-activated protein kinases/c-‍Jun amino-terminal kinases pathway, and mitochondrial energy production failure were revealed to be involved in the neurodegenerative processes. Regarding the upstream factors of these pathways, we focused on copper-derived reactive oxygen species and the disruption of calcium homeostasis. Because excess copper and zinc may be present in the synaptic clefts during ischemia, it is possible that secreted copper and copper-induced reactive oxygen species may enhance zinc neurotoxicity and eventually contribute to the pathogenesis of vascular type senile dementia.

In the production of cell-based meat, it is desirable to reduce animal-derived materials as much as possible to meet the challenges of sustainability. Here, we demonstrate the “cell sheet-based meat”: scaffold-free cell-based meat using cell sheet technology and characterize its texture and nutrients. Bovine myoblast cell sheets were prepared using temperature-responsive culture dishes (TRCDs) and 10 stacked cell sheets to fabricate three-dimensional tissue of 1.3–2.7 mm thickness. Hardness was increased by incubation on the TRCD and was further increased by boiling as is characteristic of natural meat. The wet weight percentage of total protein in the cell sheet was about half that of beef. In this method, large-sized items of cell sheet-based meat were also created by simply scaling up the TRCD. This method promises an environment-friendly food product.

To evaluate the improvements in vocal function and glottal form before and after autologous fat injection laryngoplasty in relation to the injected total fat volume in patients with unilateral vocal fold paralysis.Clinical study.Seventy-three patients with unilateral vocal fold paralysis received fat injection laryngoplasty and were divided into low-volume injection (3 mL; average, 2.0 mL) and high-volume injection (≥3 mL; average, 4.3 mL) groups. Voice function before and after fat injection laryngoplasty were examined by aerodynamics evaluations, pitch and intensity measurements, and acoustic analyses. The glottal form before and after fat injection laryngoplasty was determined by measuring the ratio of vocal fold bowing (bowing ratio) and the ratio of lengths between bilateral vocal process (width ratio) at an easy phonation under laryngeal endoscopic examination. The postoperative parameters were evaluated for a median period of four years after fat injection laryngoplasty. The differences between pre- and postoperative parameters were examined separately for each group by the paired t-test. For each variable, a comparison of the effects of surgery was conducted using an analysis of covariance model with the change between the pre- and postoperative values as a dependent variable and the preoperative value as a covariate.In both groups, all parameters of voice function and glottal form after surgery significantly improved in comparison to those before surgery. Maximum phonation time, amplitude perturbation quotient, and normalized noise energy for 0 to 4 kHz in the high-volume group improved more significantly in comparison to those in the low-volume group.As a rough guide for males, injection of more than 3 mL of autologous fat to the vocal muscle layer is recommended for reliable improvement of voice function in patients with unilateral vocal fold paralysis.

Objective We aimed to compare the changes in SARS-CoV-2 spike protein antibody titres based on age group and sex using paired blood sampling after vaccination in association with the presence of nucleocapsid protein antibody. Methods All participants were healthcare workers at Yao Municipal Hospital in Osaka who voluntarily provided peripheral blood samples (n = 636, men/women 151/485, mean age 45 years). We investigated the serial changes in SARS-CoV-2 spike protein antibody titres at 1 and 7 months after the second vaccination regarding their relationship with sex and age group. At 7 months, we also examined anti-nucleocapsid assays. Antibody titres were shown as logarithmic values and the differences were assessed using a paired or unpaired student’s t-test as appropriate. Results Among participants younger than 30 years, the antibody titres of spike protein were significantly higher in women one (p = 0.005) and seven (p = 0.038) months after vaccination. However, among those aged 30–49 years, the antibody titres were not different between the sexes at either follow-up time point. In contrast, among those aged 50–59 years, between-sex differences in antibody titres were observed only at 7 months, which was associated with a significant reduction in men. A significant negative correlation was observed between the antibody titres for spike protein at both time points in participants with positive nucleocapsid protein antibody at 7 months (r = − 0.467, p = 0.043), although a significant positive correlation was observed in those with negative results (r = 0.645, p Conclusions Between-sex differences in SARS-CoV-2 spike protein antibody titres by paired blood sampling at different time points after vaccination depended on age group. The presence of nucleocapsid protein antibody was associated with changes in spike protein antibody titres after vaccination.

Objective Sarcopenia and osteoporosis often coexist in older adults. Sarcopenia is diagnosed using the skeletal muscle mass index (SMI), which is calculated as the appendicular skeletal muscle mass (ASM)/(present height)2, although patients with osteoporosis frequently have a loss of body height. We therefore investigated whether the present height or maximum height is more useful for calculating the SMI in the evaluation of physical abilities. Methods We conducted a cross-sectional study to investigate the association of the SMI with physical abilities, such as the grip strength and gait speed, in 587 postmenopausal women. The SMI was evaluated using whole-body dual-energy X-ray absorptiometry (DXA). The SMI [(ASM)/(present height)2], modified SMI (mSMI) [(ASM)/(maximum height)2], and SMI difference (ΔSMI) (mSMI - SMI) were calculated. Results Age and body mass index (BMI)-adjusted regression analyses showed that the SMI (β=0.30, p

Trace elements such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) are absorbed from food via the gastrointestinal tract, transported into the brain, and play central roles in normal brain functions. An excess of these trace elements often produces reactive oxygen species and damages the brain. Moreover, increasing evidence suggests that the dyshomeostasis of these metals is involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, prion diseases, and Lewy body diseases. The disease-related amyloidogenic proteins can regulate metal homeostasis at the synapses, and thus loss of the protective functions of these amyloidogenic proteins causes neurodegeneration. Meanwhile, metal-induced conformational changes of the amyloidogenic proteins contribute to enhancing their neurotoxicity. Moreover, excess Zn and Cu play central roles in the pathogenesis of vascular-type senile dementia. Here, we present an overview of the intake, absorption, and transport of four essential elements (Fe, Zn, Cu, Mn) and one non-essential element (aluminum: Al) in food and their connections with the pathogenesis of neurodegenerative diseases based on metal–protein, and metal–metal cross-talk.

The complex of lysozyme with an N-acetylglucosamine tetramer shows a relatively strong hydrogen-bond network around a catalytic residue via high-resolution X-ray structural analysis. This indicates a potentially different hydrolysis mechanism to that through a glycosyl intermediate, and this is expected to be proved using neutron experiments., Lysozyme hydrolyzes the glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycans located in the bacterial cell wall. The mechanism of the hydrolysis reaction of lysozyme was first studied more than 50 years ago; however, it has not yet been fully elucidated and various mechanisms are still being investigated. One reaction system that has commonly been proposed is that the lysozyme intermediate undergoes covalent ligand binding during hydrolysis. However, these findings resulted from experiments performed under laboratory conditions using fluorine-based ligands, which facilitate the formation of covalent bonds between the ligands and the catalytic side chain of lysozyme. More recently, high-resolution X-ray structural analysis was used to study the complex of lysozyme with an N-acetylglucosamine tetramer. As a result, the carboxyl group of Asp52 was found to form a relatively strong hydrogen-bond network and had difficulty binding covalently to C1 of the carbohydrate ring. To confirm this hydrogen-bond network, neutron test measurements were successfully performed to a resolution of better than 1.9 Å.

Most of the radioactive cesium (134Cs and 137Cs), which originated from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, has remained in the soil and on plants as water-insoluble microparticles (termed as CsMPs) and maintained relatively high radioactivity levels in the district. However, it has been reported that the radioactive Cs has been absorbed by plants. To interpret this phenomenon, the authors investigated CsMPs to determine if they become soluble during filtration and dialysis experiments. Moreover, other physical properties, such as mechanical properties and thermal stability, were observed during the course of the relevant experiments. These properties can be obtained by using carbonized charcoal litter with CsMPs.

Excessive zinc ion (Zn2+) release is induced in pathological situations and causes neuronal cell death. Previously, we have reported that copper ions (Cu2+) markedly exacerbated Zn2+-induced neuronal cell death by potentiating oxidative stress, the endoplasmic reticulum (ER) stress response, and the activation of the c-Jun amino-terminal kinase (JNK) signaling pathway. In contrast, selenium (Se), an essential trace element, and amino acids containing selenium (such as seleno-l-methionine) have been reported to inhibit stress-induced neuronal cell death and oxidative stress. Thus, we investigated the effect of seleno-l-methionine on Cu2+/Zn2+-induced neuronal cell death in GT1–7 cells. Seleno-l-methionine treatment clearly restored the Cu2+/Zn2+-induced decrease in the viable cell number and attenuated the Cu2+/Zn2+-induced cytotoxicity. Accordingly, the levels of ER stress-related factors (especially, CHOP and GADD34) and of phosphorylated JNK increased upon CuCl2 and ZnCl2 co-treatment, whereas pre-treatment with seleno-l-methionine significantly suppressed these upregulations. Analysis of reactive oxygen species (ROS) as upstream factors of these pathways revealed that Cu2+/Zn2+-induced ROS production was clearly suppressed by seleno-l-methionine treatment. Finally, we found that seleno-l-methionine induced the antioxidative protein, glutathione peroxidase. Taken together, our findings suggest that seleno-l-methionine suppresses Cu2+/Zn2+-induced neuronal cell death and oxidative stress via induction of glutathione peroxidase. Thus, we think that seleno-l-methionine may help prevent refractory neurological diseases.

Vascular structures are essential for the survival of thick artificial three-dimensional (3D) tissues. However, it is difficult to create high-cell-density artificial tissue with vascular structures of a few hundred micrometers in diameter. Bioprinting technology can create artificial 3D tissues with vascular structures of a few hundred micrometers in diameter, but the cell density of bio-printed artificial 3D tissues is low. On the other hand, cell sheet technology can create high-cell-density artificial 3D tissues by stacking, but it is not possible to set small vascular structures at any place. In this study, we successfully demonstrated high-cell-density artificial 3D tissues with vascular-like structures by stacking cell sheets combined with bioprinting technology.

Although the exact pathogenesis of idiopathic pulmonary fibrosis (IPF) is still unknown, the transdifferentiation of fibroblasts into myofibroblasts and the production of extracellular matrix components such as collagen, triggered by alveolar epithelial cell injury, are important mechanisms of IPF development. In the lungs of IPF patients, apoptosis is less likely to be induced in fibroblasts than in alveolar epithelial cells, and this process is involved in the pathogenesis of IPF. We used a library containing approved drugs to screen for drugs that preferentially reduce cell viability in LL29 cells (lung fibroblasts from an IPF patient) compared with A549 cells (human alveolar epithelial cell line). After screening, we selected eperisone, a central muscle relaxant used in clinical practice. Eperisone showed little toxicity in A549 cells and preferentially reduced the percentage of viable LL29 cells, while pirfenidone and nintedanib did not have this effect. Eperisone also significantly inhibited transforming growth factor-β1-dependent transdifferentiation of LL29 cells into myofibroblasts. In an in vivo study using ICR mice, eperisone inhibited bleomycin (BLM)-induced pulmonary fibrosis, respiratory dysfunction, and fibroblast activation. In contrast, pirfenidone and nintedanib were less effective than eperisone in inhibiting BLM-induced pulmonary fibrosis under this experimental condition. Finally, we showed that eperisone did not induce adverse effects in the liver and gastrointestinal tract in the BLM-induced pulmonary fibrosis model. Considering these results, we propose that eperisone may be safer and more therapeutically beneficial for IPF patients than current therapies.

Hen egg-white lysozyme (HEWL) is an enzymatic protein with two acidic amino acids, Glu35 and Asp52, in its active site. Glu35 acts as a proton donor to the substrate and Asp52 interacts with the positively charged substrate, suggesting different protonation states of these residues. However, neutron crystallographic studies thus far have not provided a consistent picture of the protonation states of these residues. Only one study succeeded in observing the active protonation states of Glu35 and Asp52 in the triclinic crystal system. However, their active states in the most widely studied tetragonal crystal system are still unknown. The application of the D/H contrast technique in neutron crystallography improves the ability to locate exchangeable D/H atoms in proteins. In the present study, D2O and H2O solvent crystals were prepared. Each neutron data set was collected for only five days by combining a time-of-flight diffractometer (iBIX) and the spallation neutron source at the Japan Proton Accelerator Research Complex. The D/H contrast map provided better visualization of the D/H atoms in HEWL than the conventional neutron scattering length density map. The neutron D/H contrast map demonstrated the alternative protonation of the OE1 and OE2 atoms in the carboxyl group of Glu35. This alternative protonation occurs in the absence of a substrate, where high selectivity of the protonation site does not occur. In this case, only the OE1—HE1 bond attacks the substrate in an equilibrium between OE1—HE1 and OE2—HE2, or the H+ ion of the OE2—HE2 bond moves to the OE1 atom just before or after substrate binding to initiate the catalytic reaction. In contrast, the carboxyl group of Asp52 is not protonated. Protonation of the carboxyl group was not observed for other Asp and Glu residues. These results are consistent with results from NMR spectroscopy and explain the protonation states at the active site in the apo form of HEWL.

Although the pathogenesis of chronic obstructive pulmonary disease (COPD) is not yet fully understood, recent studies suggest that the disruption of the intracellular balance of oxidative (such as reactive oxygen species (ROS)) and antioxidant molecules plays an important role in COPD development and progression. Metallothionein is an endogenous metal-binding protein with reported ROS scavenging activity. Although there have been many publications on the protective effects of metallothionein in the kidney and liver, its role in COPD models such as elastase- or cigarette smoke (CS)-induced lung injury is unknown. Thus, in the present study, we analyzed the elastase-induced lung injury model using metallothionein-knockout (MT-KO; MT-1 and -2 gene deletion) mice. The expression of MT-1 and MT-2 in the lungs of MT-KO mice was markedly lower compared with that in the lungs of wildtype (WT) mice. Porcine pancreatic elastase (PPE)-induced lung injury (alveolar enlargement and respiratory impairment) was significantly exacerbated in MT-KO mice compared with WT mice. Additionally, PPE-induced increases in the number of inflammatory cells, inflammatory cytokines, and cell death in lung tissue were significantly more pronounced in MT-KO mice compared with WT mice. Finally, using an in vivo imaging system, we also found that PPE-induced ROS production in the lungs was enhanced in MT-KO mice compared with WT mice. These results suggest that metallothionein may act as an inhibitor against elastase-induced lung injury by suppressing ROS production. These results suggest that metallothionein protein, or compounds that can induce metallothionein, could be useful in the treatment of COPD.

The hole effective masses of SnS–SnSe solid solutions, crucial factors for their thermoelectric properties, are directly evaluated by ARPES measurement. They decrease slightly with increasing Se in the low Se range but sharply in the high Se range.

Renal ischemia/reperfusion (I/R) injury is a major clinical problem because it can cause acute kidney injury (AKI) or lead to the transition from AKI to chronic kidney disease (CKD). Oxidative stress, which involves the production of reactive oxygen species (ROS), plays an important role in the development and exacerbation of I/R-induced kidney injury. However, we have previously reported that lecithinized superoxide dismutase (PC-SOD), a SOD derivative with high tissue affinity and high stability in plasma, has beneficial effects in various disease models because of its inhibitory effect on ROS production. Therefore, we aimed to determine the effects of intravenous PC-SOD administration in a mouse model of renal injury induced by I/R. PC-SOD markedly ameliorated the I/R-induced increases in markers of renal damage (urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, and interleukin-6) and tubular necrosis 48 h after the intervention. We also found that PC-SOD significantly ameliorated the I/R-induced increase in ROS production, using an ex vivo imaging system. Furthermore, PC-SOD inhibited the increases in expression of markers of fibrosis (α-smooth muscle actin and collagen 1A1) 96 h after, and renal fibrosis 25 days after I/R was induced. Finally, we found that PC-SOD ameliorated the I/R-induced AKI in mice with high-fat diet-induced prediabetes. These results suggest that PC-SOD inhibits AKI and the transition from AKI to CKD through the inhibition of ROS production. Therefore, we believe that PC-SOD may represent an effective therapeutic agent for I/R-induced renal injury.

Although cancer personalized profiling by deep sequencing (CAPP-Seq) of cell-free DNA (cfDNA) has gained attention, the clinical utility of circulating tumour DNA (ctDNA) in extramammary Paget's disease (EMPD) has not been investigated. In this study, genomic alterations in the cfDNA and tumour tissue DNA were investigated in seven patients with metastatic EMPD. CAPP-Seq revealed mutations in 18 genes, 11 of which have not yet been reported in EMPD. The variant allele frequency of some of the mutated genes reflected the disease course in patients with EMPD. In one patient, the mutation was detected even though imaging findings revealed no metastasis. In another patient with triple EMPD (genital area and both axilla), cfDNA sequencing detected the mutation in a rib metastatic lesion, which was also detected in both axilla lesions but not the genital region. Investigations of the ctDNA may be useful towards the elucidation of clonal evolution in EMPD.

Conductive ceramic films, such as indium tin oxide (ITO) and zinc oxide (ZnO) thin films, are expected to be used as core semiconducting materials for applications for the Internet of Things (IoT). In this study, we focused on a nonequilibrium excitation reaction field as a bottom-up architecture, and we successfully found the basis of a technology for fabricating the above films using a plasma atmosphere and an electron beam that uniformly emits electrons within a plane as a nonequilibrium reaction field. In particular, the ZnO thin film obtained in this study exhibited good electrical properties, such as a high Hall mobility of 128.3 cm2/V, even though it was formed on a polyethylene terephthalate (PET) film substrate at room temperature. This achievement may contribute to clarifying the mechanism behind the fabrication of highly functional oxide thin films by a two-dimensional simple process without thermal treatment of the substrate during the film formation. Moreover, this technique will also enable us to provide elements for next-generation nanodevices in IoT by controlling the surface and interface of nanostructures as well as highly functional properties using complexes of metals, ceramics, and semiconductors.

Various donor muscles have been identified for restoring facial function due to longstanding facial paralysis. Donor muscles such as the gracilis and latissimus dorsi are frequently used and often produce one or two reliable vectors of force. However, there are drawbacks of using these muscles, including the instability of separating multivector functioning muscle units and limited amount of muscle contraction. Serratus anterior muscle transfer has the advantages of multiple independently functioning motor units that can be created with a single neurovascular pedicle. This article describes multivector muscle transfer using two or three superficial subslips of the serratus anterior muscle on a single neurovascular pedicle to produce an esthetic smile that is customized to imitate the function of the contralateral mimetic muscles. Twelve patients who had longstanding unilateral facial paralysis underwent muscle transfer consisting of multivector superficial subslips of the serratus anterior muscle innervated by the ipsilateral masseteric nerve. The procedure had an uneventful postoperative course, and patients obtained excellent results, with sufficient upper lip excursion, mouth angle, and lower lip working simultaneously. Functioning muscle transfer using multivector superficial subslips of the serratus anterior muscle is effective for treating longstanding facial paralysis. This technique avoids postoperative bulkiness of the cheek muscle and achieves a more natural and symmetrical smile.

Background Development of assessment tool for fracture risk is an urgent task, because bone mineral density (BMD) is less useful for evaluating fracture risk in type 2 diabetes mellitus (T2DM). Subjects and methods In total, 808 T2DM patients were enrolled in this cross-sectional study. To develop a scoring assessment tool using clinical risks for vertebral fracture (VF), we evaluated which variables were associated with VF by logistic regression analysis, and categorized these variables based on cut-off values obtained by using receiver operating characteristic (ROC) curves. For calculation of the score, the relative weight of the factors was determined, and a tentative score was assigned. Then, cut-off point of the score was examined to predict VF. Results Logistic regression analyses showed that age, diabetes duration, body mass index (BMI), serum albumin, and T score at femoral neck (FN-T score) were associated with VF risk. Parameter estimates for each risk factor obtained by logistic analyses were converted to risk scores (maximum score 23). ROC analysis showed that 8.5 was the cut-off value for detecting VF. Multiple logistic regression analysis adjusted for confounding factors showed that score ≥9 was significantly associated with an increased risk of prevalent VF (odds ratio 1.99, 95% confidence interval 1.22–3.24, p = 0.006). Conclusions This is the first study to show that a scoring assessment tool using age, duration of diabetes, BMI, serum albumin, and FN-T score is useful to estimate VF risk in patients with T2DM, being more sensitive than BMD alone in detecting bone fragility.

The radioactive cesium (134Cs and 137Cs), which originated from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, has remained in the soil and on plants as water-insoluble microparticles (termed as CsMPs) to some extent, and maintained relatively high radioactivity levels in the district. However, it has been reported that the radioactive Cs has been absorbed by plants. To interpret this phenomenon, the authors investigated CsMPs to determine if they become soluble during filtration and dialysis experiments. Moreover, other physical properties, such as mechanical properties and thermal stability, were observed during the course of the relevant experiments. These properties can be obtained by using carbonized charcoal litter with CsMPs. And simple and economic decontamination trials of the soil were performed by sieving after drying and roughly crushing.

We theoretically study low-temperature properties of the antiferromagnetic Heisenberg model with half-integer spin $S$ on the Kagome lattice with large trimerization. We have derived a low-energy effective model for general $S$ in terms of spin and nematicity operators in triangular units, and studied their low-temperature correlations for S=3/2 by classical Monte Carlo simulations. The previous study for the S=1/2 case [M. Ferrero et al., Phys. Rev. B 68, 214431 (2003)] reported a spin liquid state at low temperatures driven by a glassy behavior of isolated dimers and trimers of nematicities. The results for S=3/2 show that nematicity dimers and trimers are connected by weak links to form a defective planar network. At very low temperatures, nematicities show glassy slow dynamics, and cluster spins continue to fluctuate in a nonperiodically frozen background of nematicities. The characteristic time of glassy dynamics scales with temperature following a power law., Comment: 5 pages, 6 figures

Tin sulfide (SnS) is a compound semiconductor that has been studied for a wide range of applications, including solar cells and thermoelectric materials. In this study, the electronic structure of the SnS valence band, which is important for such applications, was investigated via angle-resolved photoelectron spectroscopy with two different excitation energies in the extreme ultraviolet region (21 and 60 eV). The contribution of the Sn 5s state to the SnS valence band was determined in relation to the k-vector by utilizing the fact that the cross section of Sn 5s state varies significantly compared to those of other states in the extreme ultraviolet region. The experimental results demonstrate that the Sn 5s state significantly contributed to the k-vector around the valence band maximum (VBM) and second VBM (VBM1).

Genomic profiling focused on the assessment of clonal evolution and intra-heterogeneity has improved the precision medicine approach in cancer treatment.1 Cancer personalized profiling by deep sequencing (CAPP-seq) of cell-free DNA (cfDNA) reveals the complexity of cancer and is a less invasive technique compared to tissue biopsy.1.

At the College of Arts and Sciences at the University of Tokyo, graphic presentation education through the use of 3D-CAD/CG is offered in the 2nd semester and descriptive geometry based on hand drawing is in the 3rd. Our interest is whether there is a difference between the spatial abilities of students who take each course. Whether each course influences the improvement of students’ spatial ability is also our concern. To get some insight into these questions, an investigation using the Mental Cutting Test (MCT) to evaluate students’ spatial ability was conducted. The results of an unpaired t-test revealed a weak significant difference between the mean scores in the MCT given to students on the first day of each course. It is suggested that the difference is due not to the improvement of students’ spatial ability during the course in the 2nd semester but rather that students with high spatial abilities tend to take the course in the 3rd semester.

The purpose of this study was to evaluate the effect of postoperative radiotherapy (RT) on temporal volume changes with a cutaneous free flap (CF) and a myocutaneous free flap (MCF). The subjects were 24 men and 11 women (mean age, 50.5 ± 15.5 years) with tongue or floor of mouth cancer. Twenty-seven cases of CF and eight cases of MCF were selected. The flap volume change of the reconstructed tongue was calculated using computed tomography (CT) images taken immediately and at one year postoperatively using the DICOM image processing software OsiriX®. The reduction rate in flap volume at one year postoperatively was 82.0 ± 15% in CF without RT, 70.3 ± 26.1% in CF with RT, 88.5 ± 14.7% in MCF without RT, and 99.5 ± 16% in MCF with RT. The MCF volume was significantly higher compared to the CF volume. Although postoperative RT reduced the CF volume by 30%, there was only a slight reduction in the MCF volume. We evaluated the effect of postoperative RT on volume reduction in 35 cases of the reconstructed tongue with CF and MCF using a computer-assisted volume rendering technique. In this study, the effect of RT on volume reduction was different between the CF and MCF.

UNSTRUCTURED The authors estimated the true number of COVID-19 infected people in Japan using the LINE questionnaire data and the PCR test results. A statistically significant correlation was observed between the infection rate per prefecture with PCR test and the rate of high fever. Using this correlation, true number of COVID-19 infected people in Japan was estimated approximately twenty thousand (±ten thousand) as of April 1, 2020.

Transthyretin (TTR) is one of more than 30 amyloidogenic proteins, and the amyloid fibrils found in patients afflicted with ATTR amyloidosis are composed of this protein. Wild-type TTR amyloids accumulate in the heart in senile systemic amyloidosis (SSA). ATTR amyloidosis occurs at a much younger age than SSA, and the affected individuals carry a TTR mutant. The naturally occurring amyloidogenic Y116S TTR variant forms more amyloid fibrils than wild-type TTR. Thus, the Y116S mutation reduces the stability of the TTR structure. A neutron diffraction experiment on Y116S TTR was performed to elucidate the mechanism of the changes in structural stability between Y116S variant and wild-type TTR through structural comparison. Large crystals of the Y116S variant were grown under optimal crystallization conditions, and a single 2.4 mm3crystal was ultimately obtained. This crystal was subjected to time-of-flight (TOF) neutron diffraction using the IBARAKI biological crystal diffractometer (iBIX) at the Japan Proton Accelerator Research Complex, Tokai, Japan (J-PARC). A full data set for neutron structure analysis was obtained in 14 days at an operational accelerator power of 500 kW. A new integration method was developed and showed improved data statistics; the new method was applied to the reduction of the TOF diffraction data from the Y116S variant. Data reduction was completed and the integrated intensities of the Bragg reflections were obtained at 1.9 Å resolution for structure refinement. Moreover, X-ray diffraction data at 1.4 Å resolution were obtained for joint neutron–X-ray refinement.

Diabetes mellitus is associated with bone fragility. Although osteoblast maturation is disturbed in patients with diabetes mellitus, the involvement of high glucose (HG) in different stages of osteoblast maturation is unclear. We used MC3T3-E1 cells, a murine osteoblastic cell line. The cells were incubated in high glucose medium (16.5 and 27.5 mM) with three different time courses: throughout 21 days, only first 7 days (early stage) and only last 7 days (late stage). Mineralization assay showed that HG throughout 21 days increased mineralization compared with control (5.5 mM). In the time course experiment, HG increased mRNA expression of Alp, osteocalcin (Ocn), runt-related transcription factor 2 and osterix on days 3 and 5. By contrast, long-term treatment with HG (14 and 21 days) decreased expression of these osteoblastic markers. HG only during early stage enhanced mineralization, while HG only during late stage had no effects. HG increased the expression of bone morphogenetic protein (BMP) 4 and enhanced phosphorylation of Smad1/5/8. Treatment with a BMP receptor antagonist LDN193189 prevented the HG-induced mineralization during early stage of osteoblast differentiation, indicating that HG in the early stage promotes mineralization by BMP4. In conclusion, the study demonstrates that continuous HG treatment might enhance early osteoblast differentiation but disturbs osteoblast maturation, and that BMP-4-Smad signal might be involved in the HG-induced differentiation and mineralization of osteoblasts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13340-020-00463-5) contains supplementary material, which is available to authorized users.

The adenosine A2B receptor is a critical protein in intestinal water secretion. In the present study, we screened compound libraries to identify inhibitors of the A2B receptor and evaluated their effect on adenosine-induced intestinal fluid secretion. The screening identified the dihydropyridine calcium antagonists nifedipine and nisoldipine. Their respective affinities for the A2B receptor (Ki value) were 886 and 1,399 nM. Nifedipine and nisoldipine, but not amlodipine or nitrendipine, inhibited both calcium mobilization and adenosine-induced cAMP accumulation in cell lines. Moreover, adenosine injection into the lumen significantly increased fluid volume in the colonic loop of wild-type mice but not A2B receptor-deficient mice. PSB-1115, a selective A2B receptor antagonist, and nifedipine prevented elevated adenosine-stimulated fluid secretion in mice. Our results may provide useful insights into the structure–activity relationship of dihydropyridines for A2B receptor. As colonic fluid secretion by adenosine seems to rely predominantly on the A2B receptor, nifedipine could be a therapeutic candidate for diarrhoea-related diseases.

The IBARAKI Biological Crystal Diffractometer (iBIX) has been available for use at MLF (Material and Life Science Facility) in J-PARC (Japan Proton Accelerator Research Complex) since 2008. The development in state-of-the-art detector systems could enable iBIX to become one of the highest-performance neutron single-crystal diffractometers in the world. Here, together with other various developments, such as data reduction software, crystal growth, and new techniques in measurement coupled analysis, we provided new hydrogen and water structural data of several proteins and macromolecules. Although the proton power at MLF has not yet reached its planned maximum (1MW), a more powerful neutron source will be soon needed for neutron protein crystallography. A future idea is also proposed and discussed in this article.

Background Recent studies have suggested that chronic kidney disease is associated with cardiovascular disease, dementia, and frailty, all of which cause disability and early death. We investigated whether increased activity of urinary N-acetyl-β-glucosaminidase (NAG), a marker of kidney injury, is associated with risk of disability or all-cause mortality in a general population. Methods Follow-up data from the Hidaka Cohort Study, a population-based cohort study of members of a Japanese rural community, were obtained via questionnaires completed by participants or their relatives. Multivariable analyses were used to investigate relations between urinary NAG activity–urinary creatinine concentration ratio and risk of disability or all-cause mortality. Results A total of 1182 participants were followed up for a median of 12.4 years. The endpoints were receipt of support under the public long-term care insurance program, and all-cause mortality. A total of 122 participants (10.3%) were reported to be receiving long-term care and 230 (19.5%) had died. After adjustment for cardiovascular risk factors along with physical activity, and using the quartile 1 results as a reference, the odds ratio (OR) for disability was 2.12 [95% confidence interval (95% confidence interval [CI]), 1.04–4.33; p = 0.038) and the hazard ratio (HR) for all-cause mortality was 1.65 (95% CI, 1.05–2.62; p = 0.031) in participants with urinary NAG/creatinine ratio in quartile 4. Similar results were obtained in participants without proteinuria: OR for disability, 2.46 (95% CI, 1.18–5.16; p = 0.017); and HR for all-cause mortality, 1.62 (95% CI, 1.00–2.63; p = 0.049). Conclusions Increased urinary NAG/creatinine ratio was associated with risk of disability or all-cause mortality in a general population.

In this study, X-ray cosα measurement was optimized with 3-axis oscillation to perform highly accurate measurements of residual stress in extruded Al alloy (A6061 and A6005C) profiles having preferred orientations and large grain sizes. In A6005C, a grain-growth region was observed just below the surface–bulk boundary and visualized via texture differences. The regions of preferred orientations corresponded well with the major changes in the residual stress as a function of depth from the surface. The boundary of the (110) and (100) textures corresponded well with the first local maximum in the von Mises stress (σvM) for both the alloys. The grain-growth region of A6005C corresponded to the region between the first and second local maxima of σvM. The principal stress (σ1) direction was almost parallel to the extrusion direction in the grain-growth region of A6005C. The changes in the σ1 direction with depth resulted in the observed anisotropic bending behavior.