Hospital physicians perform five types of work duties in Japan: An observational study

BACKGROUND: Physicians are expected to perform three unique roles as a clinician, educator, and researcher in university hospitals. However, the actual practices of physicians performing different duties are relatively unknown. Therefore, the authors conducted an observational study at a university hospital to examine physicians’ work activities. METHODS: Between 2011 and 2013, ten observers shadowed 20 physicians from different specialties for a day at the Tokyo Women’s Medical University Hospital. Observers recorded physicians’ activities every 30 seconds that were subsequently categorized into work types. The number of work types and activity changes performed by a physician in one observational period were counted. RESULTS: Authors categorized physicians’ work activities into five groups: patient care (direct and indirect), education, research, professional development, and administration. All physicians performed at least one type of activity in addition to patient care. Activity change occurred 1.86 times per hour, on average. The median time-distribution of 20 physicians was 173.8 minutes, 213.8 minutes, 3.3 minutes, 5.0 minutes, 0 minutes, and 0.8 minutes for direct patient care, indirect patient care, education, research, professional development, and administration, respectively. CONCLUSION: Japanese hospital physicians performed multiple work duties including professional development and administrative activities in addition to triple duties. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1472-6963-14-375) contains supplementary material, which is available to authorized users

Compressive force inhibits adipogenesis through COX-2-mediated down-regulation of PPARγ2 and C/EBPα

Various mechanical stimuli affect differentiation of mesoderm-derived cells such as osteoblasts or myoblasts, suggesting that adipogenesis may be also influenced by mechanical stimulation. However, effects of mechanical stimuli on adipogenesis are scarcely known. Compressive force was applied to a human preadipocyte cell line, SGBS. Levels of gene expression were estimated by real-time reverse transcription-polymerase chain reaction. The accumulation of lipids was evaluated by Sudan III or Oil Red O staining. In SGBS cells subjected to a compressive force of 226 Pa for 12 h before adipogenic induction, adipogenesis was inhibited. Compressive force immediately after adipogenic induction did not affect the adipogenesis. The expression　of peroxisome proliferator-activated receptor (PPAR) γ2 and CCAAT/enhancer binding protein (C/EBP) α mRNA during adipogenesis was inhibited by compressive force, whereas C/EBPβ and C/EBPδ mRNA levels were unaffected. In preadipocytes, compressive force increased mRNA levels of Krüppel-like factor 2, preadipocyte factor 1, WNT10b, and cyclooxygenase-2 (COX-2) which are known as negative regulators for the PPARγ2 and C/EBPα genes. Furthermore, a COX-2 inhibitor completely reversed the inhibition of adipogenesis by compressive force. In conclusion, compressive force inhibited adipogenesis by suppressing expression of PPARγ2 and C/EBPα in a COX-2-dependent manner

Role of p18INK4C in pituitary tumorigenesis

Cyclin-dependent kinase inhibitors represented by the INK4 family comprising p16INK4A, p15INK4B, p18INK4C, and p19INK4D are regulators of the cell cycle shown to be aberrant in many types of cancer. Mice lacking p18Ink4c exhibit a series of phenotypes including the development of widespread organomegaly and pituitary adenomas. The objective of our study is to examine the role of p18INK4C in the pathogenesis of human pituitary tumors. The protein and mRNA levels of p18INK4C were examined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. The methylation status of the p18INK4C gene promoter and somatic mutations of the p18INK4C gene were also investigated. p18INK4C protein expression was lost or significantly reduced in 64% of pituitary adenomas compared with levels in normal pituitary glands. p18INK4C mRNA levels were low in all ACTH adenomas and non-functioning (NF)-FSH and in 42%, 70% and 66% of GH, PRL, and subtype 3 adenomas, respectively. p18INK4C mRNA levels were significantly associated with p18INK4C protein levels. Neither methylated promoters in pituitary adenomas, except in 1 NF-FSH adenoma, nor somatic mutations of the p18INK4C gene in any pituitary adenomas were detected. The down-regulation of p18INK4C expression may contribute to the tumorigenesis of pituitary adenomas

Compressive force inhibits adipogenesis through COX-2-mediated down-regulation of PPARγ2 and C/EBPα

Various mechanical stimuli affect differentiation of mesoderm-derived cells such as osteoblasts or myoblasts, suggesting that adipogenesis may be also influenced by mechanical stimulation. However, effects of mechanical stimuli on adipogenesis are scarcely known. Compressive force was applied to a human preadipocyte cell line, SGBS. Levels of gene expression were estimated by real-time reverse transcription-polymerase chain reaction. The accumulation of lipids was evaluated by Sudan III or Oil Red O staining. In SGBS cells subjected to a compressive force of 226 Pa for 12 h before adipogenic induction, adipogenesis was inhibited. Compressive force immediately after adipogenic induction did not affect the adipogenesis. The expression　of peroxisome proliferator-activated receptor (PPAR) γ2 and CCAAT/enhancer binding protein (C/EBP) α mRNA during adipogenesis was inhibited by compressive force, whereas C/EBPβ and C/EBPδ mRNA levels were unaffected. In preadipocytes, compressive force increased mRNA levels of Krüppel-like factor 2, preadipocyte factor 1, WNT10b, and cyclooxygenase-2 (COX-2) which are known as negative regulators for the PPARγ2 and C/EBPα genes. Furthermore, a COX-2 inhibitor completely reversed the inhibition of adipogenesis by compressive force. In conclusion, compressive force inhibited adipogenesis by suppressing expression of PPARγ2 and C/EBPα in a COX-2-dependent manner

High-Trough Plasma Concentration of Afatinib Is Associated with Dose Reduction

Afatinib is used to treat non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation as a second-generation EGFR-tyrosine kinase inhibitor (TKI). Early prediction of adverse effects based on the pharmacokinetics of afatinib enables support for quality of life (QOL) in patients with no change in efficacy. We examined the pharmacokinetic relationship between trough plasma concentration and adverse effects and evaluated the utility of measuring the trough plasma concentration of afatinib as the first EGFR-TKI treatment for NSCLC in a prospective multicenter study. Twenty-four patients treated with afatinib were enrolled in this study. All blood samples were collected at the trough point, and plasma concentrations were measured using high-performance liquid chromatography–tandem mass spectrometry. Logistic regression analysis for the dose reduction of afatinib was performed, and the receiver operating characteristic (ROC) curve was plotted. Although all patients started afatinib at 40 mg/day, plasma concentrations were variable, and mean and median trough plasma concentrations were 32.9 ng/mL and 32.5 ng/mL in this study, respectively. Minimum and maximum trough plasma concentrations were 10.4 ng/mL and 72.7 ng/mL, respectively. This variability was speculated to involve personal parameters such as laboratory data. However, no patient characteristics or laboratory data examined correlated with the trough plasma concentration of afatinib, except albumin. Albumin showed a weak correlation with plasma concentration (r = 0.60, p = 0.009). The trough plasma concentration of afatinib was significantly associated with the dose reduction of afatinib (p = 0.047). The area under the ROC curve (AUC) for the trough plasma concentration of afatinib was 0.81. The cut-off value was 21.4 ng/mL. The sensitivity and specificity of the cut-off as a risk factor were 0.80 and 0.75. In summary, the trough plasma concentration of afatinib was associated with continued or reduced dosage because of the onset of several adverse effects, and a threshold was seen. Adverse effects not only lower QOL but also hinder continued treatment. Measuring plasma concentrations of afatinib appears valuable to predict adverse effects and continue effective therapy

The Impact of Aortic Valvular Calcium on Transcatheter Heart Valve Distortion

Objectives. To investigate the relationship between the eccentric calcification of aortic valve and transcatheter heart valve (THV) distortion and the impact of THV distortion on echo parameters and clinical outcomes. Background. The effects of eccentric calcification of the aortic valve on the THV distortion and the relationship between THV distortion and clinical impact were not fully understood. Methods. Patients with symptomatic severe aortic stenosis who were undergoing THV implantation were enrolled. Patients underwent preprocedural, postprocedural multislice computed tomography (MSCT), and follow-up transthoracic echocardiogram (TTE). Delta calcium score (ΔCS) is defined as the difference between the maximum and minimal calcium scores of the three cusps, while valve distortion score (VDS) is defined as the difference between the longest and shortest stent frame, as obtained using MSCT. Patients were divided into two groups according to ΔCS: “noneccentric calcification group” and “eccentric calcification group.” Results. A total of 118 patients were enrolled (59 patients in noneccentric and 59 in eccentric calcification groups). VDS was significantly lower in the noneccentric calcification group than in the eccentric calcification group (1.31 ± 0.82 mm vs. 1.73 ± 0.76 mm, p=0.004). VDS was not associated with the degree of paravalvular leak (PVL) and aortic valvular mean pressure gradient (AVPG) at 30-day and 1-year follow-up TTE and the cumulative rates of all-cause death and rehospitalization at 2-year clinical follow-up. Conclusions. Eccentric valvular calcification was associated with longitudinal THV distortion. However, THV distortion was not associated with PVL, AVPG, and adverse clinical events during midterm follow-up

Gut Microbiota and Coronary Plaque Characteristics

BACKGROUND: The relationship between gut microbiota and in vivo coronary plaque characteristics has not been reported. This study was conducted to investigate the relationship between gut microbiota and coronary plaque characteristics in patients with coronary artery disease.METHODS AND RESULTS: Patients who underwent both optical coherence tomography and intravascular ultrasound imaging and provided stool and blood specimens were included. The composition of gut microbiota was evaluated using 16S rRNA sequencing. A total of 55 patients were included. At the genus level, 2 bacteria were associated with the presence of thin-cap fibroatheroma, and 9 bacteria were associated with smaller fibrous cap thickness. Among them, some bacteria had significant associations with inflammatory/prothrombotic biomarkers. Dysgonomonas had a positive correlation with interleukin-6, Paraprevotella had a positive correlation with fibrinogen and negative correlation with high-density lipoprotein cholesterol, Succinatimonas had positive correlations with fibrinogen and homocysteine, and Bacillus had positive correlations with fibrinogen and high-sensitivity C-reactive protein. In addition, Paraprevotella, Succinatimonas, and Bacillus were also associated with greater plaque volume. Ten bacteria were associated with larger fibrous cap thickness. Some were associated with protective biomarker changes; Anaerostipes had negative correlations with trimethylamine N-oxide, tumor necrosis factor alpha, and interleukin-6, and Dielma had negative correlations with trimethylamine N-oxide, white blood cells, plasminogen activator inhibitor-1, and homocysteine, and a positive correlation with high-density lipoprotein cholesterol.CONCLUSIONS: Bacteria that were associated with vulnerable coronary plaque phenotype and greater plaque burden were identified. These bacteria were also associated with elevated inflammatory or prothrombotic biomarkers