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Skin infections caused by Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA), especially the USA300 clone, have been increasing in Japan. To prevent an epidemic of PVL-positive MRSA, rapid diagnosis and effective antimicrobial therapy are essential. However, the clinical features of, and antimicrobial efficacy against, these skin infections are not well understood in Japan. Here, we report 10 cases of skin infections caused by PVL-positive MRSA that presented over a two-year period in our clinic. Genetic analyses revealed that 90% of the PVL-positive MRSA strains were identified as USA300 and its related clones. Notably, 70% of the patients had atopic dermatitis (AD) as an underlying disease. Average durations of antimicrobial therapy for AD patients (10.6 weeks) were 2.9-fold longer than those for non-AD patients (3.7 weeks). However, all cases were improved by a long-term course of fosfomycin, minocycline, doxycycline, and/or rifampicin. Our data suggest that AD may be an important risk factor for intractable skin infections caused by PVL-positive MRSA.

Introduction Metastatic urothelial carcinomas are common in lung, liver, and lymph nodes. We present rare secondary tumor of the prostate metastasized from upper tract urothelial carcinoma. Case presentation An 87-year-old man was diagnosed as urothelial carcinoma of left upper tract and bladder. Only transurethral resection of bladder tumor was performed as palliative therapy to control hematuria. Thereafter, the tumor of left upper tract showed aggressive progression with multiple metastases involving lymph nodes and bilateral lungs. Finally, autopsy revealed swelling of left kidney due to tumor growth and systemic cancer disseminations involving bilateral lungs and renal hilar lymph nodes. In addition, prostate tumor was found incidentally. Histological examination including immunohistochemistry revealed the prostate tumor as metastatic tumor from urothelial carcinoma of left renal pelvis. Conclusion We reported rare secondary tumor of the prostate, derived from upper tract urothelial carcinoma. Further consideration would be required to provide better knowledge of the disease.

Objectives To report the effect of a selective androgen receptor modulators (SARMs) on the urethral continence mechanisms in a rat model of stress urinary incontinence (SUI) induced by bilateral ovariectomy (OVX). Materials and methods Female Sprague-Dawley rats with bilateral OVX were used. Rats were divided into five groups; sham operated, vehicle-treated OVX, low-dose SARM-treated OVX (GSK2849466A: 0.005 mg/kg/day, per os [p.o.]), high-dose SARM-treated OVX (GSK2849466A: 0.03 mg/kg/day, p.o.) and dihydrotestosterone (DHT)-treated OVX (1 mg/kg/day, subcutaneous) groups. After 4 weeks of SARM treatments or 3 weeks of DHT treatment (6 weeks after OVX), rats were subjected to evaluation of the sneeze-induced continence reflex using microtransducer-tipped catheter methods, sneeze-induced leak-point pressure, and continuous cystometry measurements, followed by histological analyses of urethral tissues. Results (i) OVX significantly impaired urethral continence function after 6 weeks to induce SUI during sneezing. (ii) Low-dose SARM treatment restored urethral baseline pressure (UBP) without affecting the amplitude of urethral response during sneezing (A-URS), partially reversing OVX-induced SUI during sneezing. (iii) High-dose SARM treatment reversed decreases in both UBP and A-URS, more effectively preventing SUI during sneezing. (iv) DHT treatment only restored A-URS without affecting UBP, partially preventing OVX-induced SUI during sneezing. (v) The high-dose SARM treatment induced hypertrophy of the striated and smooth muscle around the urethra. (vi) SARM treatment did not affect bladder function in sham or OVX rats. Conclusion Treatment with SARMs could be a more effective modality for the treatment of SUI than DHT, without affecting bladder function, by enhancing smooth- and striated muscle-mediated urethral function under stress conditions such as sneezing.

Aims The process of differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma has been progressing; however, there are no absolute immunohistochemical markers with which to definitively diagnose epithelioid mesothelioma. The aim of this study was to search for a novel negative marker of epithelioid mesothelioma. Methods and results We immunohistochemically studied the applicability of mucin 21 (MUC21), which was identified in our previous study, as a novel, negative diagnostic marker for epithelioid mesothelioma. Seventy epithelioid mesotheliomas and 70 lung adenocarcinomas were investigated for the expression of MUC21, along with other previously reported markers, by the use of immunohistochemistry. MUC21 was expressed in only two of the 70 (3%) epithelioid mesotheliomas, as compared with 67 of the 70 (96%) lung adenocarcinomas. The sensitivity, specificity and accuracy of negative MUC21 expression for differentiating epithelioid mesothelioma from lung adenocarcinoma were 97%, 96%, and 96%, respectively; these are similar to those of carcinoembryonic antigen and claudin-4, and better than those of thyroid transcription factor-1, napsin-A, and mucin 4. Conclusion MUC21 could be used as an additional, novel, negative immunohistochemical marker to differentiate mesothelioma from lung adenocarcinoma.

AIM We explored the feasibility of a long-term but low-frequency psychological preventive intervention in a high school setting. BACKGROUND High school students may experience depression; psychological interventions to improve social and cognitive skills may be useful to decrease such depression. A long-term but low-frequency intervention may be feasible in this setting because of its minimal time demands and lack of need for specialist human resources DESIGN: We conducted a single-arm longitudinal descriptive study with an intervention applied six times over 2 years in one high school. METHOD We conducted a psychological preventive intervention with 94 high school students in one school for 2 years (April 2014 to March 2016). This intervention aimed to improve social and cognitive skills. We measured social skills, cognitive distortion, and depression five times during the 2-year period, through a self-report scale. RESULTS/FINDINGS Scores for maintaining relationship skills tended to increase over the 2 years. However, depression did not decrease over the intervention period. CONCLUSION Although our research did not include control conditions and the intervention did not decrease depression, the six-session programme for high school adolescents improved an aspect of social skills that is a preventive factor against depression.

Migrating tumor cells are characterized by a sustained front-rear asymmetry, with a front enriched in filamentous actin, which is induced by Rho small GTPase Rac. Regulation of Rac activity by its regulators should be required for effective motility. Here, we show that FilGAP, a GTPase-activating protein (GAP) for Rac, controls front-rear polarity and contributes to maintain effective tumor cell migration through the extracellular matrix (ECM). Overexpression of FilGAP in breast cancer cells induced polarized morphology and led to increased migration speed in collagen matrices, while depletion of FilGAP impaired the cell polarity and migration. FilGAP localizes to the cell front through its pleckstrin-homology (PH) domain in a phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent manner and appears to inactivate Rac at its site. We found that the affinity of PH domain to PIP3 is critically involved in the maintenance of cell polarity. Moreover, small GTPase ADP-ribosylation factor 6 (Arf6), which binds to the FilGAP PH domain, also regulates FilGAP-mediated cell polarity and migration of breast cancer cells. We propose that FilGAP regulates front-rear polarity through its PIP3 and Arf6 binding in tumor cell migration through the ECM.

Recent advances in brain imaging technology have furthered our knowledge of the neural basis of auditory and speech processing, often via contributions from invasive brain signal recording and stimulation studies conducted intraoperatively. Herein, an approach for synthesizing vowel sounds straightforwardly from scalp‐recorded electroencephalography (EEG), a noninvasive neurophysiological recording method is demonstrated. Given cortical current signals derived from the EEG acquired while human participants listen to and recall (i.e., imagined) two vowels, /a/ and /i/, sound parameters are estimated by a convolutional neural network (CNN). The speech synthesized from the estimated parameters is sufficiently natural to achieve recognition rates >85% during a subsequent sound discrimination task. Notably, the CNN identifies the involvement of the brain areas mediating the “what” auditory stream, namely the superior, middle temporal, and Heschl's gyri, demonstrating the efficacy of the computational method in extracting auditory‐related information from neuroelectrical activity. Differences in cortical sound representation between listening versus recalling are further revealed, such that the fusiform, calcarine, and anterior cingulate gyri contributes during listening, whereas the inferior occipital gyrus is engaged during recollection. The proposed approach can expand the scope of EEG in decoding auditory perception that requires high spatial and temporal resolution.

Bullous pemphigoid (BP) is one of the most common autoimmune bullous diseases, that occasionally demonstrates relapse during the clinical course. However, the predictive markers for BP, that are clinically equivalent to or more useful than the anti-BP180 Abs titre, remain to be established. In this study, we analysed serum levels of multiple cytokines and TARC in BP patients to identify the predictive markers reflecting disease activity.

Background: Dabigatran is a direct thrombin inhibitor used to decrease the risk of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Its prodrug, dabigatran etexilate (DE) is often co-administrated with a proton pump inhibitor (PPI) because of its adverse effects on the gastrointestinal tract. Drug-drug interactions between DE and PPIs in daily clinical practice have not been fully elucidated. Methods: Changes in blood dabigatran concentration (DC) were investigated using the dilute thrombin time test in a randomized, open-label, two-period crossover study including 34 Japanese patients with NVAF receiving dabigatran therapy with or without PPI. Results: The average trough DC was significantly higher without PPI than with PPI (83 ± 42.3 vs. 55.5 ± 24.6 ng/mL, respectively; P < 0.001). Similarly, the average peak DC was significantly higher without PPI than with PPI (184.1 ± 107.7 vs. 124 ± 59.2 ng/mL, respectively; P = 0.0029). The average ratio of DC change at the trough and peak levels did not differ significantly among the three PPI types. Conclusions: PPI administration significantly decreased the trough and peak DCs in patients with NVAF. Therefore, when prescribing PPIs for patients with NVAF in a clinical setting, the possibility that the bioavailability of dabigatran may decrease should be considered. Keywords: Dabigatran, Proton pump inhibitor, Drugâdrug interaction

Aiming at the enhancement of electrophilicity of imino-λ3-iodanes, we have developed (tosylimino)pentafluorophenyl-λ3-iodane, which shows superior reactivity compared to the commonly used (tosylimino)phenyl-λ3-iodane in the [2+2+1]-type synthesis of imidazoles.

Aim Sodium–glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. Methods A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. Results The mean age of the patients was 73.7 ± 10.0 years. During the follow-up period (mean 289.3 days), there was no event associated with oral administration of SGLT2 inhibitors. These drugs significantly lowered fasting blood glucose and glycosylated hemoglobin levels at 6 months, and did not affect the creatinine level, blood urea nitrogen/creatinine ratio or estimated glomerular filtration rate during treatment. Although the treatment significantly increased hemoglobin and hematocrit levels, it did not affect the ultrasonographically determined diameter of the inferior vena cava, and no signs of intravascular collapse were observed. Changes in brain natriuretic peptide levels during the follow-up period were assessed in 78 patients with a brain natriuretic peptide level exceeding the normal upper limit before treatment with SGLT2 inhibitors. The brain natriuretic peptide levels significantly decreased after 6 months of treatment. Conclusions In older Japanese patients with diabetes, treatment with SGLT2 inhibitors for 6 months exerted a favorable hypoglycemic effect, while no sign of dehydration was observed. Geriatr Gerontol Int 2018; 18: 108–114.

Psoriatic arthritis (PsA), a chronic inflammatory arthropathy associated with psoriasis, is an intractable immune disorder and refractory to pharmacological intervention. We assessed efficacy of selective depletion of myeloid lineage leukocytes in patients with PsA in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were included. Eligible patients had 3 points or more in the classification criteria for PsA. Each patient received five sessions, once a week, of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® . The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders could receive an additional five GMA sessions. Of 20 patients, two did not complete the study, nine responded to five GMA sessions and nine received 10 sessions. At the first evaluation 2 weeks after the last GMA session, 13 of the 20 (65.0%) patients achieved ACR20. ACR20 was maintained in seven of 10 (70%) and five of 10 (50%) patients at the follow-up evaluation points 8 and 20 weeks after the last GMA session, respectively. GMA was well tolerated without any safety concern. This study demonstrates that GMA with the Adacolumn was effective with good safety profile in patients with PsA refractory to pharmacologicals. The results indicate a major role for myeloid leukocytes in the immunopathogenesis of PsA. A large controlled study is warranted to fully evaluate the efficacy of Adacolumn GMA in patients with PsA.

Obesity is associated with an increased risk of cardiovascular disease. C1q/TNF-related protein (CTRP)-1 is a poorly characterized adipokine that is up-regulated in association with ischemic heart disease. We investigated the role of CTRP1 in myocardial ischemia injury. CTRP1-knockout mice showed increased myocardial infarct size, cardiomyocyte apoptosis, and proinflammatory gene expression after I/R compared with wild-type (WT) mice. In contrast, systemic delivery of CTRP1 attenuated myocardial damage after I/R in WT mice. Treatment of cardiomyocytes with CTRP1 led to reduction of hypoxia-reoxygenation-induced apoptosis and lipopolysaccharide-stimulated expression of proinflammatory cytokines, which was reversed by inhibition of sphingosine-1-phosphate (S1P) signaling. Treatment of cardiomyocytes with CTRP1 also resulted in the increased production of cAMP, which was blocked by suppression of S1P signaling. The antiapoptotic and anti-inflammatory actions of CTRP1 were cancelled by inhibition of adenylyl cyclase or knockdown of adiponectin receptor 1. Furthermore, blockade of S1P signaling reversed CTRP1-mediated inhibition of myocardial infarct size, apoptosis, and inflammation after I/R in vivo. These data indicate that CTRP1 protects against myocardial ischemic injury by reducing apoptosis and inflammatory response through activation of the S1P/cAMP signaling pathways in cardiomyocytes, suggesting that CTRP1 plays a crucial role in the pathogenesis of ischemic heart disease.

The title reaction is promoted by BF3 nitrile complexes and proceeds in moderate to good yields with high regioselectivities.

Postoperative pain is a remaining issue in tonsillectomy. Polyglycolic acid (PGA) is a biocompatible material used for absorbent suture reinforcement, and its sheet has been applied for covering defects after resection of oral carcinoma. The aim of this study is to examine whether the attachment of a PGA sheet to surgical wounds would reduce posttonsillectomy pain. In this prospective single-blind study, 17 consecutive adult patients were recruited who needed to undergo tonsillectomy, mainly due to habitual tonsillitis. Following bilateral tonsillectomies, a PGA sheet was attached with fibrin glue to only 1 side, without notification to patients of which side. Postoperative pain of each side was separately evaluated with a visual analog scale at 4 time points: before each meal and before sleep. Postoperative pain of both the PGA sheet-attached and nonattached sides was most severe before breakfast among 4 time points. Postoperative pain measured before breakfast was significantly more severe in the PGA sheet-attached side than the nonattached side. As such, this study provided solid data on the negative effects of PGA sheeting on posttonsillectomy pain.

The motivation to receive rewards enhances episodic memories, and the motivation is modulated by task difficulty. In episodic retrieval, however, functional neuroimaging evidence regarding the motivation that mediates interactions between reward and task difficulty is scarce. The present fMRI study investigated this issue. During encoding performed without fMRI, participants encoded Japanese words using either deep or shallow strategies, which led to variation in difficulty level during subsequent retrieval. During retrieval with fMRI, participants recognized the target words in either high or low monetary reward conditions. In the behavioral results, a reward-related enhancement of memory was found only when the memory retrieval was difficult, and the rewarding effect on subjective motivation was greater in the retrieval of memories with high difficulty than those with low difficulty. The fMRI data showed that reward-related increases in the activation of the substantia nigra/ventral tegmental area (SN/VTA), medial temporal lobe (MTL), dorsomedial prefrontal cortex (dmPFC), and dorsolateral prefrontal cortex (dlPFC) were greater during the retrieval of memories with high difficulty than those with low difficulty. Furthermore, reward-related enhancement of functional connectivity between the SN/VTA and MTL and between the SN/VTA and dmPFC during the retrieval of memories with high difficulty was significantly correlated with reward-related increases of retrieval accuracy and subjective motivation. The reward-related enhancement of episodic retrieval and retrieval-related motivation could be most effective when the level of retrieval difficulty is optimized. Such reward-related enhancement of memory and motivation could be modulated by a network including the reward-related SN/VTA, motivation-related dmPFC, and memory-related MTL. Hum Brain Mapp 38:3428-3443, 2017. © 2017 Wiley Periodicals, Inc.

Fractures in stents are usually detected by visual analysis, which may be affected by the presence of noise and image deformations. The lack of research into automating stent fracture detection has motivated this work, in which techniques are developed to facilitate diagnosis by observation (Image Delineation Algorithm) and, when possible, to point out areas of possible fractures (Fracture Detection Algorithm). The use of classical elements and the development of additional computational techniques contributed to the process of image analysis, providing a possible way to aid medical diagnosis. The developed algorithms are applied to image samples from femoropopliteal arteries, and the results are compared to those of medical diagnosis. As a result, aside from the improvement of image display, a kappa concordance index of 0.878 for the detection of fractures confirms the method as satisfactory, with very good agreement with medical diagnosis.

Older adults are more likely than young adults to show age-related increases in remembering events that never occurred. However, little is known about the neural mechanisms underlying the increased occurrence of false alarms in older adults. To investigate this issue, this fMRI study examined age-related differences in correct rejection activations during the retrieval of memory for faces. In behavioral data, older adults showed a higher rate of false alarms than young adults in subjective recollection responses. From fMRI data, an age-related decrease in brain activations during correct rejections was identified in the inferior frontal gyrus, supramarginal gyrus, and hippocampus. In addition, interaction between activations in the inferior frontal and supramarginal regions during correct rejections was significantly lower in older adults than in young adults. These findings suggest that an age-related decline in interaction between the ventral prefrontal region, which is involved in the source monitoring process during retrieval, and the inferior parietal region, which is associated with recollection by cooperating with the hippocampus, could induce impaired differentiation between old and novel stimuli in older adults.