Insight into the population dynamics of pathogenic bacteria causing grapevine crown gall in snowfall areas: snow cover protects the proliferation of pathogenic bacteria

Grapevine crown gall (GCG) is a significant bacterial disease caused by tumorigenic Allorhizobium vitis (TAV) and is prevalent worldwide. TAV infects grapevines through wounds such as freezing injuries. Although grapevines typically avoid being wounded under snow cover, GCG occurs in many commercial vineyards in snowy regions. This study investigated the TAV population in GCG gall tissues, grapevine skins, and snow on grapevine skins from six infected vineyards located in Hokkaido, Japan, an area known for heavy snowfall. TAV was isolated not only from gall tissues but also from skins and snow on skins throughout the year. Hierarchical Bayesian model (HBM) analysis revealed that the number of TAV cells in gall tissues was affected by cultivar and low temperature, while those in skins were affected by location and low temperature. Additionally, Bayesian changepoint detection (BCD) showed that the number of TAV cells in gall and skin tissues increased during winter, including the snowfall season. Furthermore, the TAV population in grapevine skins under the snow was significantly higher than those above the snow, indicating that TAV under the snow is protected by the snow and can survive well during the snowfall season. This study highlights the ability of TAV to overwinter on/in galls and skins under the snow and act as inoculum for the next season

Plasma levels of matrix metalloproteinase‐9 (MMP‐9) are associated with cognitive performance in patients with schizophrenia

Aim: Matrix metalloproteinase‐9 (MMP‐9) has been shown to modulate synaptic plasticity and may contribute to the pathophysiology of schizophrenia. This study investigated the peripheral levels of MMP‐9 and its association with cognitive functions in patients with schizophrenia to see the possible involvement of MMP‐9 in pathophysiology of schizophrenia, especially in cognitive decline. Methods: We measured the plasma levels of MMP‐9 in 257 healthy controls and 249 patients with schizophrenia, including antipsychotic drug–free patients. We also explored the possible association between plasma MMP‐9 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition (WAIS‐ III), the Wechsler Memory Scale‐Revised (WMS‐R), and the Rey Auditory Verbal Learning Test (AVLT). Results: We found that the plasma levels of MMP‐9 were significantly higher in patients with schizophrenia, including antipsychotic drug–free patients, than in healthy controls. We found a significant negative association between plasma MMP‐9 levels and cognitive performance in controls and patients with schizophrenia. Conclusion: Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased MMP‐9 levels are associated with cognitive impairment

Plasma Levels of Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2) Are Associated with Hippocampal Volume and Cognitive Performance in Patients with Schizophrenia

Background: An imbalance in the inflammatory tumor necrosis factor system, including soluble tumor necrosis factor receptor 2 (sTNFR2), may contribute to the pathophysiology of schizophrenia. Methods: We measured the plasma levels of sTNFR2 in 256 healthy controls and 250 patients with schizophrenia including antipsychotic drug-free patients and treatment-resistant patients. We also explored the possible association between plasma sTNFR2 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, and the Rey Auditory Verbal Learning Test. An association between plasma sTNFR2 levels and hippocampal volume in controls and patients with schizophrenia was also investigated via MRI. Results: We found that the plasma levels of sTNFR2 were significantly higher in patients with schizophrenia, including both antipsychotic drug-free patients and treatment-resistant patients. We found a significant negative association between plasma sTNFR2 levels and cognitive performance in controls and patients with schizophrenia. Hippocampal volume was also negatively associated with plasma sTNFR2 levels in patients with schizophrenia. Conclusion: Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased sTNFR2 levels are associated with a smaller hippocampal volume and cognitive impairment

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Gastrointestinal Stromal Tumor Mimicking Arteriovenous Malformation of the Jejunum

There have been case reports of small intestinal gastrointestinal stromal tumors (GISTs) complicated with arteriovenous malformation (AVM) and angiodysplasia and exhibiting intense tumor staining. Herein we report a GIST of the small intestine that showed tumor staining and early venous return on imaging studies, and so the patient was suspected to have AVM. A 62-year-old male presented with intermittent pain in the left abdominal region. Contrast-enhanced computed tomography revealed a 15-mm-long spindle-shaped mass showing intense tumor staining and early venous return through the jejunal vein. In the arterial phase, the attenuation value of the tumor was 250 Hounsfield units. Color Doppler ultrasonography simultaneously delineated vessels extending from the serosal side and turbulent signals showing a mosaic pattern in the tumor. On angiography, intense staining was observed in the peripheral part of the second branch of the jejunal artery. Although these findings suggested AVM, the tumor was diagnosed as a GIST based on pathological examination of the resected specimens. In this case, no AVM or change in vascular density was noted despite the careful examination of pathological specimens, and the cause of the tumor staining remained unknown

Transoral surgery for superficial head and neck cancer: National Multi‐Center Survey in Japan

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1–75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2–357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1–113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment

EGUIDE project and treatment guidelines

Background Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. Aims The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. Method A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. Results All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. Conclusions All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists

Photodynamic Therapy Can Induce a Protective Innate Immune Response against Murine Bacterial Arthritis via Neutrophil Accumulation

Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system. Methodology/Principal Findings: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA) arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT) and preventive (Pre-PDT) effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited. Conclusions/Significance: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.National Institutes of Health (U.S.) (Grant number R01AI050875

Literature survey on epidemiology and pathology of gangliocytic paraganglioma

<p>Abstract</p> <p>Background</p> <p>Although gangliocytic paraganglioma (GP) has generally been regarded as a neuroendocrine tumor, its origin remains unclear. We therefore aimed to investigate the details of this disease by carefully analyzing and extracting common features of the disease as presented in selected publications.</p> <p>Methods</p> <p>We searched for English and Japanese cases of GP using the PubMed and IgakuChuoZasshi databases on August 2010. We then extracted and sampled raw data from the selected publications and performed appropriate statistical analyses. Additionally, we evaluated the expression of hormone receptors based on our previously reported case.</p> <p>Results</p> <p>192 patients with GP were retrieved from the databases. Patient ages ranged from 15 y to 84 y (mean: 52.3 y). The gender ratio was 114:76 (male to female, 2 not reported). Maximum diameter of the tumors ranged from 5.5 mm to 100 mm (mean: 25.0 mm). The duodenum (90.1%, 173/192) was found to be the most common site of the disease. In 173 patients with duodenal GP, gastrointestinal bleeding (45.1%, 78/173) was found to be the most common symptom of the disease, followed by abdominal pain (42.8%, 74/173), and anemia (14.5%, 25/173). Rate of lymph node metastasis was 6.9% (12/173). Our statistical analysis indicated that significant differences were found for gender between GP within the submucosal layer and exceeding the submucosal layer. Furthermore, our immunohistochemical evaluation showed that both epithelioid and pancreatic islet cells showed positive reactivity for progesterone receptors.</p> <p>Conclusions</p> <p>Our literature survey revealed that there were many more cases of GP exceeding the submucosal layer than were expected. Meanwhile, our statistical analyses and immunohistochemical evaluation supported the following two hypotheses. First, vertical growth of GP might be affected by progesterone exposure. Second, the origin of GP might be pancreatic islet cells. However, it is strongly suspected that our data have been affected by publication bias and to confirm these hypotheses, further investigation is required.</p