Migration of a Common Bile Duct Stone into the Main Pancreatic Duct due to Catheter Manipulation during Endoscopic Retrograde Cholangiopancreatography.

Introduction: We report the first case of a choledocholithiasis migrating into the main pancreatic duct (MPD) due to catheter manipulation during endoscopic retrograde cholangiopancreatography (ERCP). Case Presentation: A 57-year-old woman complaining of vomiting was diagnosed with acute cholangitis and pancreatitis due to choledocholithiasis. During ERCP, the stone migrated from the papilla into the MPD due to the pushing motion of the catheter. However, the ERCP session was completed after biliary sphincterotomy without intervention in the MPD because the migration was not noticed. The migrated stone became apparent on computed tomography the following day. The second ERCP revealed the stone measuring 5 mm in the MPD. After pancreatic sphincterotomy, a pancreatic stent was placed, which improved the obstructive pancreatitis. Conclusion: Endoscopists performing ERCP should be aware of this rare but serious complication.

Desmin immunostaining is effective for improving interobserver variability in the depth assessment of the submucosal invasion of colorectal cancers.

Tumor depth evaluation is essential for pathological tumor staging because it affects clinical management as an independent risk factor for lymph node metastasis in colorectal cancers. However, poor interobserver variability of invasion depth has been reported. This study aimed to clarify the effectiveness of desmin immunostaining in the histological diagnosis of colorectal cancer. Overall, 63 sets of slides of colorectal cancer stained with hematoxylin and eosin (H&E) and desmin were prepared and independently reviewed by four examiners. After reviewing the desmin-stained slides, the interobserver variability of H&E slides alone was significantly improved for all examiners. For the assessment of Tis vs. T1, the sensitivity and accuracy were significantly improved for all examiners by combining H&E and desmin immunostaining. For the diagnosis of T1b vs. Tis or T1a, specificity and accuracy were significantly improved by adding desmin immunostaining. Ancillary desmin staining to assess submucosal invasion in colorectal cancers significantly improved interobserver agreement, led to efficient screening of T1 cancers, and reduced excessive T1b diagnoses. The combination of desmin immunostaining and H&E staining is highly recommended for diagnosing invasive colorectal cancer.

2-Silylated Dihydroquinazolinone as a Photocatalytic Energy Transfer Enabled Radical Hydrosilylation Reagent.

The hydrosilylation of alkenes is one of the most important methods for the synthesis of organosilicon compounds. In addition to the platinum-catalyzed hydrosilylation, silyl radical addition reactions are notable as economic reactions. An efficient and widely applicable silyl radical addition reaction was developed by using 2-silylated dihydroquinazolinone derivatives under photocatalytic conditions. Electron-deficient alkenes and styrene derivatives underwent hydrosilylation to give addition products in good to high yields. Mechanistic studies indicated that the photocatalyst functioned not as a photoredox catalyst but as an energy transfer catalyst. DFT calculations clarified that the triplet excited state of 2-silylated dihydroquinazolinone derivatives released a silyl radical through the homolytic cleavage of a carbon-silicon bond, and this was followed by the hydrogen atom transfer pathway, not the redox pathway.

Comparison of the Germination Conditions of Two Large-Spore Microsporidia Using Potassium and Sodium Ion Solutions.

The germination of a microsporidian polar tube generally occurs under alkaline conditions. Typically, microsporidian spores can be stored in physiological salt solution for short periods. However, because of differences in the lodging area, the requirements may not always be uniform. In fact, Trachipleistophora sp. OSL-2012-10 (nomen nudum Trachipleistophora haruka) germinated when preserved in physiological salt solution. In this study, the germination characteristics of the large-spore microsporidia Trachipleistophora sp. FOA-2014-10 and Vavraia sp. YGSL-2015-13 were compared with those of Trachipleistophora sp. OSL-2012-10; moreover, we investigated whether these characteristics are specific to these microsporidia. We found that both microsporidia germinated in physiological salt solution. These differences in germination rates were affected by the preservation solution and temperature.

Cytosolic Glutamine Synthetase GS1;3 Is Involved in Rice Grain Ripening and Germination.

Ammonium is combined with glutamate to form glutamine. This reaction is catalyzed by glutamine synthetase (GS or GLN). Plants harbor several isoforms of cytosolic GS (GS1). Rice GS1;3 is highly expressed in seeds during grain filling and germination, suggesting a unique role in these processes. This study aimed to investigate the role of GS1;3 for rice growth and yield. Tos17 insertion lines for GS1;3 were isolated, and the nitrogen (N), amino acid, and ammonium contents of GS1;3 mutant grains were compared to wild-type grains. The spatiotemporal expression of GS1;3 and the growth and yield of rice plants were evaluated in hydroponic culture and the paddy field. Additionally, the stable isotope of N was used to trace the foliar N flux during grain filling. Results showed that the loss of GS1;3 retarded seed germination. Seeds of GS1;3 mutants accumulated glutamate but did not show a marked change in the level of phytohormones. The expression of GS1;3 was detected at the beginning of germination, with limited promoter activity in seeds. GS1;3 mutants showed a considerably decreased ripening ratio and decreased N efflux in the 12th leaf blade under N deficient conditions. The ß-glucuronidase gene expression under control of the GS1;3 promoter was detected in the vascular tissue and aleurone cell layer of developing grains. These data suggest unique physiological roles of GS1;3 in the early stage of seed germination and grain filling under N deficient conditions in rice.

Explanation of emotion regulation mechanism of mindfulness using a brain function model.

The emotion regulation mechanism of mindfulness plays an important role in the stress reduction effect. Many researchers in the fields of cognitive psychology and cognitive neuroscience have attempted to elucidate this mechanism by documenting the cognitive processes that occur and the neural activities that characterize each process. However, previous findings have not revealed the mechanism of information propagation in the brain that achieves emotion regulation during mindfulness. In this study, we constructed a functional brain model based on its anatomical network structure and a computational model representing the propagation of information between brain regions. We then examined the effects of mindfulness meditation on information propagation in the brain using simulations of changes in the activity of each region. These simulations of changes represent the degree of processing resource allocation to the neural activity via changes in the weights of each region's output. As a result of the simulations, we reveal how the neural activity characteristic of emotion regulation in mindfulness, which has been reported in previous studies, is realized in the brain. Mindfulness meditation increases the weight of the output from each region of the thalamus and sensory cortex, which processes sensory stimuli from the external world. This sensory information activates the insula and anterior cingulate cortex (ACC). The orbitofrontal cortex and dorsolateral prefrontal cortex inhibit amygdala activity (i.e., top-down emotion regulation). However, when mindfulness meditation dominates bottom-up processing via sensory stimuli from the external world, amygdala activity increases through the insula and ACC activation.

Long-term Outcomes of Therapeutic Endoscopic Retrograde Cholangiopancreatography for Choledocholithiasis in Patients ≥90 Years Old: A Multicenter Retrospective Study.

Objective The safety and prognosis of complete stone removal for the treatment of choledocholithiasis in older patients are unknown. This multicenter retrospective study assessed the outcomes of complete stone removal in elderly patients (≥90 years) with respect to the prognosis. Methods We divided patients who underwent endoscopic cholangiopancreatography for choledocholithiasis into two groups: complete stone removal or incomplete stone removal with plastic stent insertion. The patient characteristics, adverse events, number of endoscopic cholangiopancreatographies, overall survival rates, and disease-specific cumulative death were compared between the groups. Patients Two hundred and twenty-three participants ≥90 years old were included in the study, including 48 (22%) men and 175 (78%) women. The median age was 92 (range, 90-104) years old. There were 160 (72%) and 63 (28%) patients in the complete and incomplete groups, respectively. Results The age, performance status, comorbidities, severe complication rates, and stone diameter were comparable between the groups. The proportion of patients with at least 5 stones was significantly higher in the incomplete group than in the complete group [complete group: 8.1% (13/160) and incomplete group: 21% (13/63), p<0.01]. The overall survival rate was significantly higher in the complete group (p<0.01), while the disease-specific cumulative death rate was higher in the incomplete group (p<0.01). Conclusion Complete stone removal for choledocholithiasis may contribute to a better prognosis in elderly patients ≥90 years old.

Bioprinting 3D human cardiac tissue chips using the pin type printer 'microscopic painting device' and analysis for cardiotoxicity.

In this study, three-dimensional (3D) cardiac tissue constructed using the pin type bioprinter 'microscopic painting device' and layer-by-layer cell coating technique was confirmed to have drug responsiveness by three different analytical methods for cardiotoxicity assay. Recently, increasing attention has been focused on biofabrication to create biomimetic 3D tissue. Although various tissues can be produced in vitro, there are many issues surrounding the stability and reproducibility of the preparation of 3D tissues. Thus, although many bioprinters have been developed, none can efficiently, reproducibly and precisely produce small 3D tissues (µm-mm order) such as spheroids, which are most commonly used in drug development. The 3D cardiac tissue chips were successfully constructed with a similar number of cells as conventional 2D tissue using a pin type bioprinter, and corresponding drug-induced cardiotoxicities were obtained with known compounds that induce cardiotoxicity. The 3D cardiac tissue chips displayed uniform cell density and completely synchronized electrophysiological properties as compared to 2D tissue. The 3D tissues constructed using a pin type bioprinter as a biofabrication device would be promising tools for cardiotoxicity assay as they are capable of obtaining stable and reproducible data, which cannot be obtained by 2D tissue.

Is complete stone removal for choledocholithiasis always necessary in extremely elderly patients?

BACKGROUND AND AIM: Endoscopic stone removal has some complications. Although the life expectancy of elderly patients has increased dramatically worldwide, little information is available on the necessity of complete endoscopic stone removal in extremely elderly patients. This study aimed to evaluate the safety and efficacy of complete endoscopic stone removal in extremely elderly patients. METHODS: All extremely elderly patients (>90 years) who underwent endoscopic stone removal for choledocholithiasis at our hospital between January 2012 and January 2017 were retrospectively evaluated. The included patients were divided into complete stone removal and incomplete stone removal groups. Complication rate, overall survival (OS), and disease-specific survival (DSS) rates were compared between the two groups. RESULTS: Overall, 73 patients were included in this study. The median number of stones was one (range, 0-10) and two (range, 1-12) (P = 0.043), while the median diameter of the largest stones was 9 (range, 0-27) and 14 (range, 5-46) mm (P = 0.001) in the complete and incomplete stone removal groups, respectively. During the follow-up period, OS was 60% and 39% and DSS was 95% and 97% in the complete and incomplete stone removal groups, respectively. Kaplan-Meier analysis found no significant difference in OS and DSS between the two groups (P = 0.052 and P = 0.646, respectively). CONCLUSION: Complete stone removal might not always be necessary in extremely elderly patients aged ≥90 years.

Three-dimensional bioprinting human cardiac tissue chips of using a painting needle method.

Three-dimensional (3D) printers are attracting attention as a method for arranging and building cells in three dimensions. Bioprinting technology has potential in tissue engineering for the fabrication of scaffolds, cells, and tissues. However, these various printing technologies have limitations with respect to print resolution and due to the characteristics of bioink such as viscosity. We report a method for constructing of 3D tissues with a "microscopic painting device using a painting needle method" that, when used with the layer-by-layer (LbL) cell coating technique, replaces conventional methods. This method is a technique of attaching the high viscosity bioink to the painting needle tip and arranging it on a substrate, and can construct 3D tissues without damage to cells. Cell viability is the same before and after painting. We used this biofabrication device to construct 3D cardiac tissue (LbL-3D Heart) using human-induced pluripotent stem cell-derived cardiomyocytes. The constructed LbL-3D Heart chips had multiple layers with a thickness of 60 µm, a diameter of 1.1 mm, and showed synchronous beating (50-60 beats per min). The aforementioned device and method of 3D tissue construction can be applied to various kinds of tissue models and would be a useful tool for pharmaceutical applications.

Correlation between spinal and pelvic movements during gait and aggravation of low back pain by gait loading in lumbar spinal stenosis patients.

BACKGROUND: Lumbar alignment of posterior or anterior tilts affects the exacerbation and remission of symptoms of lumbar spinal stenosis patients. This study aimed to clarify the correlation between spinal and pelvic movements during gait and the aggravation of low back pain after gait loading in lumbar spinal stenosis patients. METHODS: A total of 29 patients with lumbar spinal stenosis completed leg and low back pain assessments and gait analysis before and after gait loading tests. Patients were divided into leg and low back pain change (n = 8), leg pain only change (n = 12), and non-change (n = 9) groups based on the differences of leg and low back pain between before and after the tests. Peak kinematic values of the anterior tilts of the trunk, thoracic spine, lumbar spine, and pelvis during the stance phase were obtained via three-dimensional gait analysis. RESULTS: In the leg and low back pain change group, the anterior lumbar and pelvic tilts were larger after than before the tests; however, in the leg pain only change and non-change groups, only the anterior lumbar tilt was larger after than before the tests. Anterior lumbar tilt before and after the tests negatively correlated with the aggravation of low back pain, and an increase in the anterior pelvic tilt positively correlated with the aggravation of low back pain. CONCLUSIONS: In lumbar spinal stenosis patients, smaller anterior lumbar tilt and larger anterior pelvic tilt during gait loading may affect the aggravation of low back pain by gait loading. Increasing in lumbar lordosis during gait might be one of the factors leading to low back pain in lumbar spinal stenosis patients.

Galectin-3 and N-acetylglucosamine promote myogenesis and improve skeletal muscle function in the mdx model of Duchenne muscular dystrophy.

The muscle membrane, sarcolemma, must be firmly attached to the basal lamina. The failure of proper attachment results in muscle injury, which is the underlying cause of Duchenne muscular dystrophy (DMD), in which mutations in the dystrophin gene disrupts the firm adhesion. In patients with DMD, even moderate contraction causes damage, leading to progressive muscle degeneration. The damaged muscles are repaired through myogenesis. Consequently, myogenesis is highly active in patients with DMD, and the repeated activation of myogenesis leads to the exhaustion of the myogenic stem cells. Therefore, approaches to reducing the risk of the exhaustion are to develop a treatment that strengthens the interaction between the sarcolemma and the basal lamina and increases the efficiency of the myogenesis. Galectin-3 is an oligosaccharide-binding protein and is known to be involved in cell-cell interactions and cell-matrix interactions. Galectin-3 is expressed in myoblasts and skeletal muscle, although its function in muscle remains elusive. In this study, we found evidence that galectin-3 and the monosaccharide N-acetylglucosamine, which increases the synthesis of binding partners (oligosaccharides) of galectin-3, promote myogenesis in vitro. Moreover, in the mdx mouse model of DMD, treatment with N-acetylglucosamine increased muscle-force production. The results suggest that treatment with N-acetylglucosamine might mitigate the burden of DMD.-Rancourt, A., Dufresne, S. S., St-Pierre, G., Lévesque, J.-C., Nakamura, H., Kikuchi, Y., Satoh, M. S., Frenette, J., Sato, S. Galectin-3 and N-acetylglucosamine promote myogenesis and improve skeletal muscle function in the mdx model of Duchenne muscular dystrophy.

Characteristics of thoracic and lumbar movements during gait in lumbar spinal stenosis patients before and after decompression surgery.

BACKGROUND: Although gait analysis has been previously conducted for lumbar spinal stenosis patients, the vertebral segmental movements, such as of the thoracic and lumbar regions, and whether the spinal movement during gait changes after decompression surgery remain unclear. METHODS: Ten patients with lumbar spinal stenosis and 10 healthy controls participated. Clinical outcomes were assessed using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and Visual Analogue Scale. Spinal kinematic data of the participants during gait were acquired using a three-dimensional motion analysis system. The trunk (whole spine), thoracic, and lumbar flexion and pelvic tilting values were calculated. Spinal kinematic data and clinical outcomes were collected preoperatively and 1month postoperatively for the patients. FINDINGS: Compared to that observed preoperatively, the clinical outcomes significantly improved at 1month postoperatively. In the standing position, the preoperative lumbar extension of the patients was significantly smaller than that of the controls. Moreover, during gait, the lumbar flexion relative to the standing position of the patients was smaller than that of the controls preoperatively, and increased at 1month postoperatively. The sum of the thoracic and lumbar flexion values during gait negatively correlated with the score for leg pain. INTERPRETATION: The epidural pressure of lumbar spinal stenosis patients is known to be higher than that of normal subjects during gait, and to decrease during walking with lumbar flexion. Preoperatively, smaller thoracic and lumbar flexion movements during gait relative to the standing position cannot decrease epidural pressure; as a result, severe leg pain might be induced.

Urodynamic findings in patients with Creutzfeldt-Jakob disease: a case report.

AIM OF STUDY: Urinary dysfunction in Creutzfeldt-Jakob disease (CJD) patients is attributed to functional incontinence, since they often have immobility and loss of motivation. In contrast, previously no urodynamic findings are available in CJD patients. CASE REPORT: We had 2 CJD patients who had urinary frequency and urinary retention. We performed urodynamics with the spouse's informed consent in order to explore the mechanism of urinary dysfunction in those cases. Case 1 had typical acute cognitive deterioration with incontinence and urinary retention, while case 2 had subacute cognitive deterioration (that started after admission) and nocturia. The urodynamic findings were diverse. One feature was detrusor overactivity during bladder filling in case 1. Another feature of urodynamic finding includes neurogenic change of sphincter EMG in case 1 and decreased bladder sensation in case 2. CONCLUSION: Urodynamics in our two CJD patients revealed detrusor overactivity and neurogenic sphincter electromyogram, presumably reflecting pathological lesions in the prefrontal cortex/basal ganglia as well as the sacral spinal cord in CJD.