Presence of ectopic germinal center structures in autoimmune hepatitis.

Autoimmune tissues may contain ectopic germinal centers (EGCs). However, these structures have never been described in the liver of patients suffering from autoimmune hepatitis (AIH). We retrospectively reviewed histological features of 120 definite AIH cases, and found 10 cases harboring markers of EGCs. In these cases, CD21+ follicular dendritic cells were intermixed with CD3+ T and CD20+ B lymphocytes. The latter expressed the GC-specific marker bcl6, and some were proliferative as assessed by Ki67 expression. Antibody-secreting cells (ASCs) defined by expression of the mum-1 transcription factor and presence of cytoplasmic IgMs were usually present in the periphery of these structures, but some were also present within the EGCs. Notably, some ASCs were IgG-switched. Common treatment applied to AIH patients achieved biochemical normalization as efficiently as in patients without EGCs. In the present study, we provide the proof for the occurrence of functional EGCs enabling differentiation of B cells into ASCs and occurrence of immunoglobulin switch in AIH livers.

Migration Stimulating Factor (MSF): Its Role in the Tumour Microenvironment.

Migration Stimulating Factor (MSF) is a 70 kDa truncated isoform of fibronectin (FN); its mRNA is generated from the FN gene by an unusual two-stage processing. Unlike full-length FN, MSF is not a matrix molecule but a soluble protein which displays cytokine-like activities not displayed by any other FN isoform due to steric hindrance. There are two isoforms of MSF; these are referred to as MSF+aa and MSF-aa, while the term MSF is used to include both.MSF was first identified as a motogen secreted by foetal and cancer-associated fibroblasts in tissue culture. It is also produced by sprouting (angiogenic) endothelial cells, tumour cells and activated macrophages. Keratinocytes and resting endothelial cells secrete inhibitors of MSF that have been identified as NGAL and IGFBP-7, respectively. MSF+aa and MSF-aa show distinct functionality in that only MSF+aa is inhibited by NGAL.MSF is present in 70-80% of all tumours examined, expressed by the tumour cells as well as by fibroblasts, endothelial cells and macrophages in the tumour microenvironment (TME). High MSF expression is associated with tumour progression and poor prognosis in all tumours examined, including breast carcinomas, non-small cell lung cancer (NSCLC), salivary gland tumours (SGT) and oral squamous cell carcinomas (OSCC). Epithelial and stromal MSF carry independent prognostic value. MSF is also expressed systemically in cancer patients, being detected in serum and produced by fibroblast from distal uninvolved skin. MSF-aa is the main isoform associated with cancer, whereas MSF+aa may be expressed by both normal and malignant tissues.The expression of MSF is not invariant; it may be switched on and off in a reversible manner, which requires precise interactions between soluble factors present in the TME and the extracellular matrix in contact with the cells. MSF expression in fibroblasts may be switched on by a transient exposure to several molecules, including TGFß1 and MSF itself, indicating an auto-inductive capacity.Acting by both paracrine and autocrine mechanisms, MSF stimulates cell migration/invasion, induces angiogenesis and cell differentiation and alters the matrix and cellular composition of the TME. MSF is also a survival factor for sprouting endothelial cells. IGD tri- and tetra-peptides mimic the motogenic and angiogenic activities of MSF, with both molecules inhibiting AKT activity and requiring αvß3 functionality. MSF is active at unprecedently low concentrations in a manner which is target cell specific. Thus, different bioactive motifs and extracellular matrix requirements apply to fibroblasts, endothelial cells and tumour cells. Unlike other motogenic and angiogenic factors, MSF does not affect cell proliferation but it stimulates tumour growth through its angiogenic effect and downstream mechanisms.The epithelial-stromal pattern of expression and range of bioactivities displayed puts MSF in the unique position of potentially promoting tumour progression from both the "seed" and the "soil" perspectives.

Molecular detection of fungal and bacterial DNA from pustules in patients with palmoplantar pustulosis: special focus on Malassezia species.

BACKGROUND: Palmoplantar pustulosis (PPP) is a distinct, chronic skin disorder characterized by intraepidermal pustules on the palms and soles. It is hypothesized that microorganisms on the skin might induce the symptoms of PPP via inflammatory cell activation. However, the microbiota has not been studied in detail because of the assumption that the pustules in PPP are sterile. AIM: To elucidate the role of microorganisms in pathogenesis of PPP. METHODS: PCR analysis was performed of microbial DNA fragments in the pustules of patients with PPP. The sequence of the D1/D2 LSU 26s rRNA gene and that of the 16S rRNA gene was used for fungal and bacterial DNA detection, respectively. RESULTS: In total, 71 samples were carefully collected from the pustules of patients with PPP. Fungal DNA bands were detected in 68 samples, and fungi including Malassezia spp. were identified in 30 of 71 samples (42.3%). Malassezia restricta was the most frequently encountered fungus (14/71; 19.7%). However, bacterial DNA was not detected by the methods used. Furthermore, identical fungal DNA was not detected in the outer lid of the pustules, suggesting that the fungi detected within the pustule did not derive from contamination via the skin surface. CONCLUSIONS: In the present study, we demonstrated for the first time that certain pustules in patients with PPP contain fungal DNA fragments, especially those of Malassezia spp. Our findings provide new insights on the role of skin microbiota in the pathogenesis of PPP.

Extended-spectrum beta-lactamase-producing Escherichia coli harbouring sul and mcr-1 genes isolates from fish gut contents in the Mekong Delta, Vietnam.

This study investigated the existence of sulfonamides and colistin resistance genes among extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli recovered from fish gut in Vietnam and evaluated the susceptibility patterns of the ESBL-producing E. coli to relevant antimicrobials. A total of 88 ESBL-producing E. coli isolates were analysed for the presence of the ESBLs, sul (1, 2, 3) and mcr (1-3) genes by PCR. Antimicrobial resistance phenotypes of isolates were determined by disc diffusion. Results showed that: (i) A high prevalence of 94·3% of sulfonamide resistance was observed in 88 isolates. Moreover, the existence of 2·3% of ESBL-producing E. coli harbouring mcr-1 gene were detected; (ii) The phylogenetic types A and B1 were most frequent, and the blaCTX-M group1 and blaTEM genes encoding ESBL were detected in 47·7% of the isolates; (iii) ESBL-producing E. coli harbouring mcr-1 gene exhibited resistance to 11 antibiotics. The existence of mcr-1 and sul1,2,3 genes and the extremely high level of multiple drug resistance in all ESBL-producing E. coli isolates obtained from sampled fish in Vietnam is a major concern. Therefore, it is imperative to monitor ESBL-producing E. coli in the river waters of Vietnam.

Centrifugal lipodystrophy of the scalp manifesting as centrifugal lipodystrophic alopecia.

Centrifugal lipodystrophy (CLD), characterized by a depressed lesion in the abdominal skin, is a chronic disease occurring more often among younger patients of East Asian descent. We present an extremely unusual case of CLD of the scalp associated with reversible hair loss. The patient demonstrated alopecia in the frontal, temporal and occipital areas of the scalp, which connected to form a ring-shaped area of hair loss. Curiously, the area of hair loss gradually expanded outwards while the central region showed normal hair regrowth. Immunohistochemical analysis demonstrated reduced expression of leptin, an adipokine capable of inducing the anagen phase of the hair cycle, in the adipose tissue, associated with active inflammation. By contrast, recovery of leptin expression was observed at sites of healed inflammatory lesions, suggesting that reversible hair loss might be caused by a change in leptin expression in adipose tissue.

Pyloroplasty may reduce weight loss 1 year after esophagectomy.

Weight loss after esophagectomy is common and is associated with unfavorable prognosis. However, the clinical features and surgical methods that influence postesophagectomy weight loss are not well characterized. This study aims to determine those features (especially the surgical methods) that may affect postoperative weight loss. We reviewed 221 esophageal cancer patients who had undergone esophagectomy at Kumamoto University Hospital (Kumamoto, Japan) between November 2012 and June 2015. Among these, we recruited 106 patients who had undergone transthoracic esophagectomy with gastric conduit reconstruction, had no cancer recurrence within 1 year, and no missing follow-up data. We tabulated the body weight changes and risk factors associated with weight loss exceeding 10% at 1-year postesophagectomy. The mean body weights at baseline and 1-year postsurgery were 60.3 kg (standard error (SE): 0.91) and 52.6 (SE: 0.91), respectively. One year postsurgery, the body weights had changed as follows: mean: -12.2%; median: -12.9%; standard deviation: 9.06; range: -36.1-18.56%; interquartile range: -10.5 to -14.0%. In the multivariate logistic regression analysis, the absence of pyloroplasty was the sole risk factor for more than 10% weight loss (OR: 3.22; 95% CI: 1.08-11.9; P = 0.036). Our data suggest that pyloroplasty with esophagectomy can overcome the post-surgical weight loss.

Minimally invasive esophagectomy may contribute to long-term respiratory function after esophagectomy for esophageal cancer.

Evidence suggests that minimally invasive esophagectomy has several advantages with regard to short-term outcomes, compared to open esophagectomy in esophageal cancer patients. However, the impact of minimally invasive esophagectomy on long-term respiratory function remains unknown. The objective of this study is to assess the association between use of the minimally invasive esophagectomy and long-term respiratory dysfunction in esophageal cancer patients after esophagectomy. This retrospective single institution study using prospectively collected data included 87 consecutive esophageal cancer patients who had undergone esophagectomy. All patients underwent a respiratory function test before, and one year after esophagectomy. Logistic regression analysis was used to compute the hazard ratio for long-term respiratory dysfunction. Minimally invasive esophagectomies were performed in 53 patients, and open esophagectomies in 34 patients. The two groups showed no significant differences in terms of postoperative complications and postoperative course. Nor were any differences observed between the two groups in terms of volume capacity (L) and forced expiratory volume 1.0 (L) before esophagectomy (P > 0.34). However, one year after esophagectomy, the decreases in volume capacity and forced expiratory volume 1.0 were significantly less in the minimally invasive esophagectomy group than in the open esophagectomy group (P = 0.04 and P = 0.007, respectively). Multivariate analyses revealed that minimally invasive esophagectomy was an independent favorable factor for maintenance of forced expiratory volume 1.0 (hazard ratio = 0.17, 95% confidence interval 0.04-0.71; P = 0.01). Minimally invasive esophagectomy may be an independent favorable factor for maintenance of long-term respiratory function in esophageal cancer patients after esophagectomy.

Monitoring sputum culture in resected esophageal cancer patients with preoperative treatment.

Pneumonia is a major cause of postesophagectomy mortality and worsens the long-term survival in resected esophageal cancer patients. Moreover, preoperative treatments such as chemotherapy or chemoradiotherapy (which have recently been applied worldwide) might affect the bacterial flora of the sputum. To investigate the association among preoperative treatments, the bacterial flora of sputum, and the clinical and pathological features in resected esophageal cancer patients, this study newly investigates the effect of preoperative treatments on the bacterial flora of sputum. We investigated the association among preoperative treatments, the bacterial flora of sputum, and clinical and pathological features in 163 resected esophageal cancer patients within a single institution. Pathogenic bacteria such as Candida (14.1%), Staphylococcus aureus (6.7%), Enterobacter cloacae (6.1%), Haemophilus parainfluenzae (4.9%), Klebisiella pneumoniae (3.7%), Methicillin-resistant Staphylococcus aureus (MRSA) (3.7%), Pseudomonas aeruginosa (2.5%), Escherichia coli (1.8%), Streptococcus pneumoniae (1.8%), and Haemophilus influenzae (1.2%) were found in the sputum. The pathogen detection rate in the present study was 34.3% (56/163). In patients with preoperative chemotherapy and chemoradiotherapy, the indigenous Neisseria and Streptococcus species were significantly decreased (P= 0.04 and P= 0.04). However, the detection rates of pathogenic bacteria were not associated with preoperative treatments (all P> 0.07). There was not a significant difference of hospital stay between the sputum-monitored patients and unmonitored patients (35.5 vs. 49.9 days; P= 0.08). Patients undergoing preoperative treatments exhibited a significant decrease of indigenous bacteria, indicating that the treatment altered the bacterial flora of their sputum. This finding needs to be confirmed in large-scale independent studies or well-designed multicenter studies.

Bilateral effects of hospital patient-safety procedures on nurses' job satisfaction.

AIM: The aim of this study was to examine how hospital patient-safety procedures affect the job satisfaction of hospital nurses. Additionally, we investigated the association between perceived autonomy and hospital patient-safety procedures and job satisfaction. BACKGROUND: Recently, measures for patient safety have been recognized as an essential requirement in hospitals. Hospital patient-safety procedures may enhance the job satisfaction of nurses by improving the quality of their work. However, such procedures may also decrease their job satisfaction by imposing excessive stress on nurses because they cannot make mistakes. METHODS: The participants included 537 nurses at 10 private hospitals in Japan (The surveys were collected from March to July 2012). Factors related to hospital patient-safety procedures were demonstrated using factor analysis, and the associations between these factors and nurses' self-perceived autonomy and job satisfaction were examined using structural equation modelling. FINDINGS: Five factors regarding hospital patient-safety procedures were extracted. Additionally, structural equation modelling revealed statistically significant associations between these factors and the nurses' self-perceived autonomy and job satisfaction. The findings showed that nurses' perceived autonomy of the workplace enhanced their job satisfaction and that their perceptions of hospital patient-safety procedures promoted their job satisfaction. However, some styles of chief nurses' leadership regarding patient safety restrict nurses' independent and autonomous decision-making and actions, resulting in a lowering of job satisfaction. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study demonstrated that hospital patient-safety procedures have ambiguous effects on nurses' job satisfaction. In particular, chief nurses' leadership relating to patient safety can have a positive or negative effect on nurses' job satisfaction. The findings indicated that hospital managers should demonstrate positive attitudes to improve patient safety for nurses' job satisfaction. In addition, policymakers in the hospitals should consider that chief nurses' leadership styles may reduce autonomy and suppress nurses' job satisfaction.

Chiral Surface Twists and Skyrmion Stability in Nanolayers of Cubic Helimagnets.

Theoretical analysis and Lorentz transmission electron microscopy (LTEM) investigations in an FeGe wedge demonstrate that chiral twists arising near the surfaces of noncentrosymmetric ferromagnets [Meynell et al., Phys. Rev. B 90, 014406 (2014)] provide a stabilization mechanism for magnetic Skyrmion lattices and helicoids in cubic helimagnet nanolayers. The magnetic phase diagram obtained for freestanding cubic helimagnet nanolayers shows that magnetization processes differ fundamentally from those in bulk cubic helimagnets and are characterized by the first-order transitions between modulated phases. LTEM investigations exhibit a series of hysteretic transformation processes among the modulated phases, which results in the formation of the multidomain patterns.

Laser frequency locking with 46 GHz offset using an electro-optic modulator for magneto-optical trapping of francium atoms.

We demonstrate frequency offset locking between two laser sources using a waveguide-type electro-optic modulator (EOM) with 10th-order sidebands for magneto-optical trapping of Fr atoms. The frequency locking error signal was successfully obtained by performing delayed self-homodyne detection of the beat signal between the repumping frequency and the 10th-order sideband component of the trapping light. Sweeping the trapping-light and repumping-light frequencies with keeping its frequency difference of 46 GHz was confirmed over 1 GHz by monitoring the Doppler absorption profile of I2. This technique enables us to search for a resonance frequency of magneto-optical trapping of Fr.

Long-term outcome of esophagectomy for primary malignant melanoma of the esophagus: a single-institute retrospective analysis.

Primary malignant melanoma of the esophagus (PMME) is a highly malignant tumor with a poor prognosis. Because PMME is an extremely rare disease, therapeutic strategies against the tumor have yet to be established, and the efficacy of esophagectomy remains unclear. The objective of this study was to evaluate the post-esophagectomy survival of PMME patients. Ten patients who underwent esophagectomy for PMME between March 2005 and April 2013 at the Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan, were identified from the institutional database. We retrospectively retrieved clinical information and data on the long-term outcomes from the patients' records. Survival rates after esophagectomy were calculated by the Kaplan-Meier method, and the hazard ratios of mortality were determined using the Cox's model. A follow-up study of the 10 patients revealed 7 cancer recurrences and 5 deaths. Median survival time was 34.5 months, and 5 of 10 patients survived longer than 2 years. The 1-year disease-free survival rate was 40%, and the 1- and 3-year overall survival rates were 70% and 60%, respectively. Importantly, all three of the non-relapsing patients were histologically confirmed as free of lymph node involvement. The four patients with lymph node metastasis relapsed within 1 year. The disease-free survival was significantly shorter in patients with lymph node involvement than in those without lymph node involvement (univariate hazard ratio = 13.3, 95% confidence interval 1.85-266.4; P = 0.009). In conclusion, esophagectomy might benefit PMME patients with no lymph node metastasis. Further large-scale cohort studies are needed to establish the treatment strategy for PMME.

Prognostic and clinical impact of sarcopenia in esophageal squamous cell carcinoma.

Recently, depletion of skeletal muscle mass (sarcopenia) has been linked to poor prognosis in several types of cancers, but has not been investigated in esophageal squamous cell carcinoma (ESCC). This retrospective study investigates the relationship between sarcopenia and clinical outcome in ESCC patients treated by surgical resection or definitive chemoradiation therapy (dCRT). The study was retrospectively conducted in a single academic hospital in Kumamoto, Japan, and involved 325 ESCC patients (256 surgical cases and 69 dCRT cases) treated between April 2005 and April 2011. Skeletal muscle mass was quantified by radiologic measures using standard computed tomography scans. The skeletal muscle tissue in the 325 ESCC patients was distributed as follows: mean: 47.10; median: 46.88; standard deviation (SD): 7.39; range: 31.48-71.11; interquartile range, 46.29-47.90. Skeletal muscle tissue was greater in male patients than in female patients (P < 0.0001), but was independent of other clinical and tumor features. Sarcopenia was not significantly associated with overall survival (log rank P = 0.54). Lymph node involvement significantly altered the relationship between sarcopenia and survival rate (P for interaction = 0.026). Sarcopenia significantly reduced the overall survival of patients without lymph node involvement (log rank P = 0.035), but was uncorrelated with overall survival in patients with lymph involvement (log rank, P = 0.31). The anastomosis leakage rate was significantly higher in the sarcopenia group than in the non-sarcopenia group (P = 0.032), but other surgical complications did not significantly differ between the two groups. Sarcopenia in ESCC patients without lymph node involvement is associated with poor prognosis, indicating sarcopenia as a potential biomarker for identifying patients likely to experience an inferior outcome. Moreover, sarcopenia was associated with anastomosis leakage but no other short-term surgical outcome.

Further improvement of the upper limit on the direct 3α decay from the Hoyle state in 12C.

The direct 3α decay branch from the 02+ state at Ex=7.65 MeV in 12C, which is known as the Hoyle state, is considered to affect the triple-α reaction rate strongly and to give crucial information on its structure. We have performed a high-precision measurement of the 3α decay from this state using the 12C(12C,3α)12C reaction at E12C=110 MeV. The branching ratio of the direct 3α decay was under the detection limit in the present experiment. By comparing with Monte Carlo simulations for three decay mechanisms as the sequential decay through the ground state of ^{8}Be, the direct decay with equal energies of three α particles, and the direct decay to the phase space uniformly, we have obtained the upper limit of 0.2% on the direct 3α decay.

α-Amylase is a potential growth inhibitor of Porphyromonas gingivalis, a periodontal pathogenic bacterium.

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is a major etiological agent in the development and progression of periodontal diseases. In this study, we isolated a cell growth inhibitor against P. gingivalis species from rice protein extract. MATERIAL AND METHODS: The cell growth inhibitor active against P. gingivalis was purified from polished rice extract using a six-step column chromatography process. Its antimicrobial properties were investigated through microscope analysis, spectrum of activity and general structure. RESULTS: The inhibitor was identified as AmyI-1, an α-amylase, and showed significant cell growth inhibitory activity against P. gingivalis species. Scanning electron microscopy micrograph analysis and bactericidal assay indicated an intriguing possibility that the inhibitor compromises the cell membrane structure of the bacterial cells and leads to cell death. Moreover, α-amylases from human saliva and porcine pancreas showed inhibitory activity similar to that of AmyI-1. CONCLUSIONS: This is the first study to report that α-amylases cause cell death of periodontal pathogenic bacteria. This finding highlights the potential importance and therapeutic potential of α-amylases in treating periodontal diseases.

Reduction of dental metallic artefacts in CT: value of a newly developed algorithm for metal artefact reduction (O-MAR).

AIM: To evaluate the image quality of O-MAR (Metal Artifact Reduction for Orthopedic Implants) for dental metal artefact reduction. MATERIALS AND METHODS: This prospective study received institutional review board approval and written informed consent was obtained. Thirty patients who had dental implants or dental fillings were included in this study. Computed tomography (CT) images were obtained through the oral cavity and neck during the portal venous phase. The system reconstructed the O-MAR-processed images in addition to the uncorrected images. CT attenuation and image noise of the soft tissue of the oral cavity were compared between the O-MAR and the uncorrected images. Qualitative analysis was undertaken between the two image groups. RESULTS: The image noise of the O-MAR images was significantly lower than that of the uncorrected images (p < 0.01). O-MAR offered plausible attenuations of soft tissue compared with non-O-MAR. Better qualitative scores were obtained in the streaking artefacts and the degree of depiction of the oral cavity with O-MAR compared with non-O-MAR. CONCLUSION: O-MAR enables the depiction of structures in areas in which this was not previously possible due to dental metallic artefacts in qualitative image analysis. O-MAR images may have a supplementary role in addition to uncorrected images in oral diagnosis.