Difficulties Facing Junior Physicians and Solutions Toward Delivering End-of-Life Care for Patients with Cancer: A Nationwide Survey in Japan

Background: Junior physicians' perceived difficulty in end-of-life care of patients with cancer has not been structurally investigated; therefore, current challenges and solutions in this area remain unknown. Objectives: To identify some difficulties junior physicians face in delivering end-of-life care for patients with cancer and to clarify the support required to reduce these difficulties. Design: A nationwide survey was conducted in over 300 institutions selected randomly from 1037 clinical training hospitals in Japan. Participants: From each of these institutions, two resident physicians of postgraduate year (PGY) 1 or 2, two clinical fellows of PGY 3–5, and an attending physician were requested to respond to the survey. Measurements: The survey investigated issues regarding end-of-life care using the palliative care difficulties scale with two additional domains (“discussion about end-of-life care” and “death pronouncement”). Items related to potential solutions for alleviating the difficulties as well were investigated. Results: A total of 198 resident physicians, 134 clinical fellows, and 96 attending physicians responded to the survey (response rate: 33.0%, 22.3%, and 32.0%). The results revealed that junior physicians face difficulties within specific domains of end-of-life care. The most challenging domain comprised communication and end-of-life discussion with patients and family members, symptom alleviation, and death pronouncement. The most favored supportive measure for alleviating these difficulties was mentorship, rather than educational opportunities or resources regarding end-of-life care. Conclusion: The findings of this study reveal the need for further effort to enrich the mentorship and support systems for junior physicians delivering end-of-life care

The Structural Complexity of the Human BORIS Gene in Gametogenesis and Cancer

BORIS/CTCFL is a paralogue of CTCF, the major epigenetic regulator of vertebrate genomes. BORIS is normally expressed only in germ cells but is aberrantly activated in numerous cancers. While recent studies demonstrated that BORIS is a transcriptional activator of testis-specific genes, little is generally known about its biological and molecular functions.Here we show that BORIS is expressed as 23 isoforms in germline and cancer cells. The isoforms are comprised of alternative N- and C-termini combined with varying numbers of zinc fingers (ZF) in the DNA binding domain. The patterns of BORIS isoform expression are distinct in germ and cancer cells. Isoform expression is activated by downregulation of CTCF, upregulated by reduction in CpG methylation caused by inactivation of DNMT1 or DNMT3b, and repressed by activation of p53. Studies of ectopically expressed isoforms showed that all are translated and localized to the nucleus. Using the testis-specific cerebroside sulfotransferase (CST) promoter and the IGF2/H19 imprinting control region (ICR), it was shown that binding of BORIS isoforms to DNA targets in vitro is methylation-sensitive and depends on the number and specific composition of ZF. The ability to bind target DNA and the presence of a specific long amino terminus (N258) in different isoforms are necessary and sufficient to activate CST transcription. Comparative sequence analyses revealed an evolutionary burst in mammals with strong conservation of BORIS isoproteins among primates.The extensive repertoire of spliced BORIS variants in humans that confer distinct DNA binding and transcriptional activation properties, and their differential patterns of expression among germ cells and neoplastic cells suggest that the gene is involved in a range of functionally important aspects of both normal gametogenesis and cancer development. In addition, a burst in isoform diversification may be evolutionarily tied to unique aspects of primate speciation

In situ 4D distribution visualization of carbon-black volume fraction in cathode slurry of lithium-ion battery by multi-layered electrical resistance tomography (mlERT)

In situ 4D (3D spatial + 1D temporal) distribution of carbon black (CB) volume fraction /CB in cathode slurry of lithium-ion battery (LIB) (CB powder and lithium cobalt dioxide (LiCoO 2) particles in NMP/PVDF solution) has been visualized by multi-layered electrical resistance tomography (mlERT). The mlERT are composed of 24 electrodes (=8 electrodes/layer 3 layers) with a newly developed multiplexer unit, which reconstructs the normalized conductivity r from the measured voltages U. The conditions of /CB is observed in the three dispersion states which are initial state, dispersing state, and fully dispersed state, under the mixing time t ¼ 0 360s and the mixing speed x ¼ 720; 400; and 200rpm. As the results, in the initial state (t ¼ 0s), the distribution of /CB is clearly visualized by the spatial r distribution from the high conductivity of /CB to the low conductivity of /Li which represents the initial position of CB powder and LiCoO 2 particles in NMP/PVDF solution. In the dispersing state (t ¼ 30 120 s), the distribution of /CB is dynamically changed as the r distribution is graduallly increased in the 3D spatial domain of mlERT which represents the dispersing CB powder within LiCoO2 particles in NMP/PVDF solution. In the fully dispersed state (t ¼ 120 360 s), the /CB is in the uniformity as the r distribution tends to be uniformly dispersed which represents the fully dispersed CB in cathode slurry. In order to evaluate the distribution visualization of /CB in the fully dispersed state by mlERT, a qualitatively-scanning electron microscope (SEM) and a quantitatively-invasive two-wire resistance measurement are tested. The qualitatively-SEM images of fully dispersed CB at the height z ¼ 5 and 20mm are observed in the distributed formation of CB powder within LiCoO2 particles in NMP/PVDF solution which agrees to the uniformity of the r distribution by mlERT. Moreover, the comparison of r distribution by mlERT to the quantitatively-invasive two-wire resistance measurement is resulted in a low root means square error RSME ¼ 0:00196% which indicates the high accuracy of the in situ 4D distribution visualization of /CB in cathode slurry of LIB by mlERT

IMQ-induced psoriatic mouse skin has an abundance of SLURP1.

<p>IMQ or control cream was applied daily to the shaved backs for BALB/c mice. (A) Phenotypical presentation of mouse back skin after 2 or 4 days of IMQ treatment. (B) Immunofluorescent staining of vehicle or IMQ cream-treated mouse skin using an anti-SLURP1 antibody. Dashed lines indicate the border between the epidermis and dermis. Scale bars = 50 μm. The experiments were repeated six times with similar results. (C) Quantification of <i>IL-22</i> and <i>SLURP1</i> mRNA expression in skin from mice treated for 2 days with IMQ. Bars depict the mean ± S.D. (n = 6) of fold-changes in mRNA copy number normalized to GPADH and quantified relative to control. *p < 0.05, **p < 0.01 vs. control (Student’s t-test).</p