[Infective Endocarditis Caused by Abiotrophia defectiva Required Double-valve Replacement Using the Manouguian Procedure].

A 39-year-old man was presented with infective endocarditis caused by Abiotrophia defectiva. Transesophageal echocardiography revealed extensive vegetation and destruction extending from the aortic valve to the aortic-mitral curtain and mitral valve accompanied by severe regurgitation of the aortic and mitral valves. After removal of vegetation, double-valve replacement were performed with double patch and mechanical prosthesis using the manouguian procedure.

Identification and Validation of Combination Plasma Biomarker of Afamin, Fibronectin and Sex Hormone-Binding Globulin to Predict Pre-eclampsia.

The purpose of the present study was to identify a plasma protein biomarker able to predict pre-eclampsia (PE). Comprehensive quantitative proteomics using mass spectrometry with sequential window acquisition of all theoretical fragment ion spectra (SWATH-MS) was applied to plasma samples of 7 PE and 14 healthy pregnant women (for PE subjects, plasma samples were taken before onset of PE), and 11 proteins were selected as candidates potentially able to differentiate the two groups. Plasmas collected at gestational weeks 14-24 from 36 PE and 120 healthy pregnant women (for PE subjects, plasma samples were taken before onset of PE) were used to conduct selected reaction monitoring quantification analysis, optimize protein combinations and conduct internal validation, which consisted of 30 iterations of 10-fold cross-validation using multivariate logistic regression and receiver operating characteristic (ROC) analysis. The combination of afamin, fibronectin, and sex-hormone-binding globulin was selected as the best candidate. The 3-protein combination predictive model (predictive equation and cut-off value) generated using the internal validation subjects was successfully validated in another group of validation subjects (36 PE and 54 healthy (for PE subjects, plasma samples were taken before onset of PE)) and showed good predictive performance, with the area under the curve (AUC) 0.835 and odds ratio 13.43. In conclusion, we newly identified a 3-protein combination biomarker and established a predictive equation and cut-off value that can predict the onset of PE based on analysis of plasma samples collected during gestational weeks 14-24.

Association between statin use and cancer: data mining of a spontaneous reporting database and a claims database.

PURPOSE: In recent years, the potential risk of cancer associated with statin use has been a focus of much interest. However, it remains uncertain whether statin therapy is associated with cancer risk. To examine the association between statin use and the risk of cancer, we conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and a large organized database of claims constructed by a database vendor (The Japan Medical Data Center Co., Ltd, Tokyo, Japan [JMDC]). METHODS: Relevant reports in the FAERS, which included data from the first quarter of 2004 through the end of 2012, were identified and analyzed. The reporting odds ratio (ROR) was used to detect spontaneous report signals and was calculated using the case/non-case method. Additionally, signals were detected via the information component (IC) using the IC025 metric. Furthermore, event sequence symmetry analysis (ESSA) was applied to identify the risk of cancer following treatment with statins over the period January 2005 to July 2013. RESULTS: In the FAERS database analyses, significant signals for colorectal cancer and pancreatic cancer were found for statins as a class. In the ESSA, significant associations between statin use and colorectal cancer and pancreatic cancer were found, with adjusted sequence ratios (95% confidence intervals) of 1.20 (1.08-1.34) and 1.31 (1.13-1.53), respectively, at an interval of 48 months. CONCLUSIONS: Multi-methodological approaches using different algorithms and databases suggest that statin use is associated with an increased risk for colorectal cancer and pancreatic cancer.

Association of statin use with storage lower urinary tract symptoms (LUTS): data mining of prescription database.

OBJECTIVE: The efficacy and safety of statins have been studied in a number of clinical trials and epidemiological studies. In recent years, the Medicine and Healthcare Products Regulatory Agency (MHRA) has assessed the evidence available on the following adverse reactions associated with the use of statins: sleep disturbances, memory loss, micturition disorders (problems with urination), sexual disturbances, depression, and interstitial pneumopathy. However, the association between statin use and the risk of these adverse reactions remains unclear. To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) or the disorder causing LUTS, we carried out data mining using a prescription database. METHODS: A large organized database of prescriptions constructed by a database vendor was used in the study. Symmetry analysis was used to identify the risk of LUTS after using statins over the period January 2006 to August 2013. Statin use in combination with drugs administered for storage LUTS was examined by prescription sequence symmetry analysis (PSSA). RESULTS: A significant association between statins and drugs for storage LUTS was found, with adjusted sequence ratios (ASRs) of 1.21 (95% CI, 1.00 - 1.46), 1.19 (95% CI, 1.04 - 1.38), and 1.17 (95% CI, 1.05 - 1.30) for intervals of 91, 182, and 365 days, respectively. In the analyses of individual statins, significant associations were found only for pravastatin. Significant associations with individual drugs for storage LUTS were found for solifenacin succinate with ASRs of 1.36 (95% CI, 1.02 - 1.81), 1.48 (95% CI, 1.19 - 1.84), and 1.47 (95% CI, 1.25 - 1.73) for intervals of 91, 182, and 365 days, for flavoxate hydrochloride with an ASR of 1.56 (95% CI, 1.13 - 2.17) at an interval of 182 days, and for oxybutynin hydrochloride with ASRs of 2.06 (95% CI, 1.11 - 3.94) and 1.71 (95% CI, 1.09 - 2.72) at intervals of 182 and 365 days. Significant associations with gender were found only in females with ASRs of 1.25 (95% CI, 1.04 - 1.51) and 1.23 (95% CI, 1.07 - 1.41) at intervals of 182 and 365 days, respectively. CONCLUSIONS: Analysis of the prescription database showed significant association for storage LUTS in statin users.

Primary care physicians working in rural areas provide a broader scope of practice: a cross-sectional study.

BACKGROUND: Scope of practice (SoP) is an important factor for primary care physicians (PCPs). One of the strong determinants of SoP is rurality. Although Japan has several rural areas, the SoP in rural areas and the effect of rurality on SoP have not been investigated. This study aimed to describe SoP in Japanese primary care settings and examine the association between rurality and SoP. METHODS: This cross-sectional study included PCPs in Japan. The participants were randomly sampled from the mailing list of the Japan Primary Care Association. The Scope of Practice Inventory (SPI) and Scope of Practice for Primary Care (SP4PC) were used as indicators of SoP. The Rurality Index for Japan (RIJ) was used for rurality. This study compared the number of items of SPI (total score, inpatient care, urgent care and ambulatory care) and SP4PC experienced by > 80% of all PCPs in the most urban (RIJ:1-10) and rural areas (RIJ: 91-100). A multivariable linear regression analysis was also performed to examine the relationship between the RIJ and SPI/SP4PC. RESULTS: Of 1,000 potential participants, 299 physicians responded to the survey (response rate: 29.9%). PCPs in the most rural areas experienced a greater number of items in the inpatientl/urgent care domains of the SPI and SP4PC than those in the most urban areas. The RIJ was the only common factor for a broader SoP in both the SPI and SP4C models. The coefficients of SoP were 0.09 (95% confidence interval: 0.03-0.16) in the SPI model and 0.017 (0.005-0.03) in the SP4PC model. CONCLUSION: Rurality was considerably associated with SoP. The findings of this study will be helpful in understanding the SoP on rural and urban areas.

Autophagy in tobacco BY-2 cells cultured under sucrose starvation conditions: isolation of the autolysosome and its characterization.

Tobacco culture cells carry out a large-scale degradation of intracellular proteins in order to survive under sucrose starvation conditions. We have previously suggested that this bulk degradation of cellular proteins is performed by autophagy, where autolysosomes formed de novo act as the major lytic compartments. The digestion process in autolysosomes can be retarded by addition of the cysteine protease inhibitor E-64c to the culture medium, resulting in the accumulation of autolysosomes. In the present study, we have investigated several properties of autolysosomes in tobacco cells. Electron microscopy showed that the autolysosomes contain osmiophilic particles, some of which resemble partially degraded mitochondria. It also revealed the presence of two kinds of autolysosome precursor structures; one resembled the isolation membrane and the other the autophagosome of mammalian cells. Immunofluorescence microscopy showed that autolysosomes contain acid phosphatase, in accordance with cytochemical enzyme analyses by light and electron microscopy in a previous study. Autolysosomes isolated by cell fractionation on Percoll gradients showed the localization of acid phosphatase, vacuolar H(+)-ATPase and cysteine protease. These results show that starvation-induced autophagy in tobacco cells follows a macroautophagic-type response similar to that described for other eukaryotes. However, our results indicate that, although the plant vacuole is often described as being equivalent to the lysosome of the animal cell, a new low pH lytic compartment-the autolysosome-also contributes to proteolytic degradation when tobacco cells are subjected to sucrose deprivation.

Comparative genomics approach to the expression of figalpha, one of the earliest marker genes of oocyte differentiation in medaka (Oryzias latipes).

We analyzed molecular cascades of sex differentiation in medaka gonads by examining the transcriptional regulation of the oocyte-expressed gene, figalpha. We first confirmed that figalpha is one of the earliest marker genes of oocyte differentiation by quantitative RT-PCR and in situ hybridization. Expression of putative figalpha target genes, zpc4 and zpb, followed that of figalpha. A meiosis-specific gene, scp3, showed expression temporally and spatially similar to figalpha. To characterize the cis-regulatory sequences of figalpha, we compared genomic organizations of vertebrate figalpha genes. Both number and sequence homology of the C-terminal exons showed divergence, suggesting their less important roles. In the frog, Xenopus tropicalis, and in many teleosts, figalpha is located between hexokinase 2 and beta-adducin. We compared this genomic region for potential cis-regulatory elements and found no DNA stretches with high homology. In spite of this lack of sequence similarities, fluorescent protein transgenes surrounded with figalpha flanking sequences from the compact genomes of fugu or Tetraodon faithfully reproduced the endogenous expression of figalpha in the medaka oocytes, indicating conserved regulatory mechanisms.