Comparison of intra-individual coefficients of variation on the paired sampling data when inter-individual variations are different between measures

Additional file 2. Supplemental figures for the pain intensity data (residual plots, P–P plots and Cook’s distance against leverage/(1-leverage))

Early Start of Chemotherapy after Resection of Primary Colon Cancer with Synchronous Multiple Liver Metastases: A Case Report

The start of chemotherapy treatment usually requires a delay of about 4 weeks after surgical resection in patients with primary colorectal cancer and synchronous distant metastasis. However, there is no evidence to indicate the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. Here, we present a case in which combination chemotherapy with capecitabine and oxaliplatin (XELOX) was started within 1 week after a right hemicolectomy for synchronous multiple liver metastases. To our knowledge, this is the first report of the start of chemotherapy, involving treatments such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and XELOX, within 1 week after a colorectal cancer operation with anastomosis. The findings suggest possible changes in the start time of chemotherapy after surgery in the future

Cyclosporine A and FK506 as Potent Inhibitors of Streptococcus intermedius Intermedilysin-Induced NFAT-1 Activation

Cyclosporine A (CsA) and tacrolimus (FK506), a member of calcineurin inhibitors, inhibit inflammation process as part of immune response. Nuclear activated T cells subfamily NFAT1 is a trascription factor responsible for the regulation of immune response genes. Streptococcus intermedius, an oral commensal bacterium, has been shown to strongly associate with liver abscess.  The S. intermedius strains produce intermedilysin (ILY), which is responsible for the bacterial virulence. Cyclosporine A and FK506 have been widely used to control NFAT activation in most of cell types, however the ability of CsA and FK506 to inhibit ILY-induced NFAT1 activation remains to be investigated. The aim of this study was to investigate the effect of CsA and FK506 on NFAT1 activation caused by ILY. Human cholangiocellular cell line HuCCT1 was stimulated with various concentrations of ILY. The cell and nuclear morphological change was observed by microscopy analysis. The NFAT1 nuclear translocation that indicates its activation was detected by immunocytochemistry. The inhibitory effect of CsA and FK506 was tested after 30 min application before ILY treatment by using immunofluorescence microscope. The results showed cell and nuclear shrinkage in ILY-treated cells. The NFAT1 was translocated to the nuclei in HuCCT1 cells, and observed in dose dependent manner.  Cyclosporine A and FK506 inhibited ILY-induced NFAT1 nuclear translocation.  In conclusion, CsA and FK506 may act as potent inflammation control agents in S. intermedius ILY-infected cells.Keywords: Cyclosporine A, FK506, NFAT1, intermedilysi

Suppressive effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of Candida species and MRSA to acrylic denture resin

Objectives: The effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of microorganisms such as non-Candida albicans Candida (NCAC) and methicillin-resistant Staphylococcus aureus (MRSA), frequently detected in oral infections in immunocompromised and/or elderly people, to denture resin material, are still unclear. Here, we report the effects of MPC-polymer on the adherence of C. albicans, NCAC, and MRSA to acrylic denture resin. Methods: Sixteen strains of C. albicans, seven strains of C. glabrata, two strains of C. tropicalis, one strain of C. parapsilosis, and six strains of MRSA were used. We cultured the fungal/bacterial strains and examined the cell growth and adherence of fungi/bacteria to mucin-coated acrylic denture resin plates (ADRP) with or without MPC-polymer coating, by scanning electron microscopy. The cell surface hydrophobicity of the fungal/bacterial strains was measured by the adsorption to hydrocarbons. Results: MPC-polymer did not affect the growth of all strains of Candida species and MRSA, but significantly suppressed adherence to ADRP in most strains of C. albicans and all strains of NCAC and MRSA. A significant positive correlation was found between cell hydrophobicity and the reduction rates of microbial adherence to ADRP treated with 5% of MPC-polymer. Conclusions: MPC-polymer treatment for acrylic resin material suppresses the adherence of C. albicans, NCAC and MRSA via their hydrophilicity interaction. Clinical significance: The application of MPC-polymer for denture hygiene is potent to prevent oral candidiasis, denture stomatitis and opportunistic infection, caused by Candida species and MRSA, via suppressing the adherence of those fungus/bacteria

Individual Radiation Exposure Dose Due to Support Activities at Safe Shelters in Fukushima Prefecture

Immediately after the accidents in the nuclear power stations in Fukushima on March 11, the Japanese Government ordered the evacuation of the residents within a 20-km radius from the station on March 12, and asked various institutions to monitor the contamination levels of the residents. Hirosaki University, which is located 355 km north of Fukushima City, decided to send support staff to Fukushima. This report summarizes the results of the exposure of 13 individual teams from March 15 to June 20. The support teams surveyed more than 5,000 people during this period. Almost all subjects had external contamination levels of less than 13 kcpm on Geiger-Müller (GM) survey meter, which is categorized as “no contamination level.” The 1st team showed the highest external exposure dose, but the 4th team onward showed no significant change. Subsequently, the internal radiation exposure was measured using a whole body counter that indicated undetectable levels in all staff members. Although the measured external radiation exposure dose cannot have serious biological effects on the health of an individual, a follow-up study of the residents in Fukushima and other regions where the radioactive material has spread will be required for a long time

An immune-adrenergic pathway induces lethal levels of platelet-activating factor in mice

Acute immune responses with excess production of cytokines, lipid/chemical mediators, or coagulation factors, often result in lethal damage. In addition, the innate immune system utilizes multiple types of receptors that recognize neurotransmitters as well as pathogen-associated molecular patterns, making immune responses complex and clinically unpredictable. We here report an innate immune and adrenergic link inducing lethal levels of platelet-activating factor. Injecting mice with toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS), cell wall N-glycans of Candida albicans, and the α₂-adrenergic receptor (α₂-AR) agonist medetomidine induces lethal damage. Knocking out the C-type lectin Dectin-2 prevents the lethal damage. In spleen, large amounts of platelet-activating factor (PAF) are detected, and knocking out lysophospholipid acyltransferase 9 (LPLAT9/LPCAT2), which encodes an enzyme that converts inactive lyso-PAF to active PAF, protects mice from the lethal damage. These results reveal a linkage/crosstalk between the nervous and the immune system, possibly inducing lethal levels of PAF

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls

Pathogenic variants in highly penetrant genes are useful for the diagnosis, therapy, and surveillance for hereditary breast cancer. Large-scale studies are needed to inform future testing and variant classification processes in Japanese. We performed a case-control association study for variants in coding regions of 11 hereditary breast cancer genes in 7051 unselected breast cancer patients and 11,241 female controls of Japanese ancestry. Here, we identify 244 germline pathogenic variants. Pathogenic variants are found in 5.7% of patients, ranging from 15% in women diagnosed <40 years to 3.2% in patients ≥80 years, with BRCA1/2, explaining two-thirds of pathogenic variants identified at all ages. BRCA1/2, PALB2, and TP53 are significant causative genes. Patients with pathogenic variants in BRCA1/2 or PTEN have significantly younger age at diagnosis. In conclusion, BRCA1/2, PALB2, and TP53 are the major hereditary breast cancer genes, irrespective of age at diagnosis, in Japanese women

ピオグリタゾン トウヨ ニヨル フクブ ダイドウミャクリュウ ニオケル コウドウミャク コウカ サヨウ

Accumulating evidence suggests that inflammatory cytokines secreted from visceral fat tissues potentially promote atherosclerosis progression. Recent reports suggested that pioglitazone, which is an anti-diabetes drug, reduces expression of tumor necrosis factor（TNF）‐α and ameliorates insulin-resistance in diabetic mice. Pioglitazone was also reported to suppress progression of coronary atherosclerosis. The objective of this study is to assess the effect of pioglitazone on inflammatory changes in abdominal aortic aneurysms（AAAs）. This study protocol was approved by the medical ethics committee in Tokushima University Hospital. Patients with AAA were randomized into two groups. One was with pioglitazone（Group P）. The other was without pioglitazone（Group C）. Biopsy specimens were obtained from the abdominal subcutaneous fat, the greater omentum, the retroperitoneal periaortic fat and the aneurysmal wall. Immunohistochemistry of CD ６８in those specimens was performed. The number of macrophages in Group P was lower than that in Group C. Expressions of inflammatory cytokines in those specimens were evaluated by real-time quantitative reverse transcription-polymerase chain reaction analysis. Expression of inflammatory cytokines in Group P were reduced, when compaird with those in Group C. Our data may suggest that pioglitazone reduce inflammatory changes in human aortic aneurysm

A proposed core curriculum for dental English education in Japan

Background: Globalization of the professions has become a necessity among schools and universities across the world. It has affected the medical and dental professions in terms of curriculum design and student and patient needs. In Japan, where medicine and dentistry are taught mainly in the Japanese language, profession-based courses in English, known as Medical English and Dental English, have been integrated into the existing curriculum among its 83 medical and 29 dental schools. Unfortunately, there is neither a core curriculum nor a model syllabus for these courses. Methods: This report is based on a survey, two discussion forums, a workshop, and finally, the drafting of a proposed core curriculum for dental English approved by consensus of the participants from each university. Results: The core curriculum covers the theoretical aspects, including dental English terms and oral pathologies; and practical aspects, including blended learning and dentist-patient communication. It is divided into modules and is recommended to be offered for at least two semesters. Conclusions: The core curriculum is expected to guide curriculum developers in schools where dental English courses are yet to be offered or are still in their early development. It may also serve as a model curriculum to medical and dental schools in countries in Asia, Europe, Africa, and Central and South America, where English is not the medium of instruction

Lymphocyte subset characterization associated with persistent hepatitis C virus infection and subsequent progression of liver fibrosis

This study aims to deepen understanding of lymphocyte phenotypes related to the course of hepatitis C virus (HCV) infection and progression of liver fibrosis, in a cohort of atomic-bomb survivors. The study subjects comprise three groups: 162 HCV persistently infected, 145 spontaneously cleared, and 3511 uninfected individuals. We found increased percentages of peripheral blood TH1 and total CD8 T cells and decreased percentages of NK cells in the HCV persistence group, compared with the other two groups, after adjustment for age, gender, and radiation exposure dose. Subsequently, we found that increased TH1 cell percentages in the HCV persistence group were significantly associated with an accelerated time-course reduction in platelet counts―accelerated progression of liver fibrosis―while TC1 and NK cell percentages were inversely associated with the progression. This study suggests that TH1 immunity is enhanced by persistent HCV infection, and that percentages of peripheral TH1, TC1, and NK cells may help predict progression of liver fibrosis.This research was based on RERF Research Protocols 3-09, 4-02, 2-00, 9-92, and was supported in part by the U.S. National Institute of Allergy and Infectious Diseases (NIAID Contract HHSN272200900059C)