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"Niwa, Keiko"
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The secret world of Arrietty : picture book
A family of miniature people who live beneath the floor of a country house, borrowing things they need from the humans, are forced to leave their home when their teen-aged daughter, Arietty, is seen by a human.
Book
Associations between emotional intelligence, empathy and personality in Japanese medical students
Background
It is known that empathic communication is important for physicians to achieve higher patient satisfaction and health outcomes. Emotional intelligence (EI), empathy and personality in medical students predict students’ individual disposition and their emotional and empathic perceptions. This study aimed to investigate: 1) The association between empathy, EI and personality, and 2) Gender differences in the association between empathy, EI and personality.
Method
Participants were 357 1st year medical students from 2008 to 2011 at one medical school in Japan. Students completed self-report questionnaires comprising three validated instruments measuring EI: Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF), empathy: Jefferson Scale of Physician Empathy- student version (JSPE) and personality: NEO-Five-Factor Inventory (NEO-FFI), which explores 5 dimensions of personality Neuroticism (N), Extraversion (E), Openness to experience (O), Agreeableness (A), and Conscientiousness (C).
Results
Pearson Correlations showed weak association between TEIQue-SF and JSPE. TEIQue-SF and NEO-FFI showed positive correlation for E and C, and strong negative correlation for N and weak positive correlation for A and O. Weak positive correlation between JSPE and the NEO-FFI were observed for E and A. Although effect sizes were small, N, A and empathy were significantly higher in females (unpaired t-test). However, hierarchical multiple-regression analysis when controlling for gender and personality showed no association between EI, empathy and gender. A, TEIQue-SF and N were found to make small contributions in respect of predictions for JSPE. Personality contributed significantly to the prediction of TEIQue-SF. N had the largest independent negative contribution (β = − 0,38).
Conclusion
In our study population of 1st year medical students, females had significantly higher N, A and empathy scores than males. Medical students’ N score was strongly negatively associated with EI. Empathy was weakly associated with EI and A. However, when controlling gender and personality in regression analysis, gender did not affect EI and empathy, rather personality is the most important factor. Our findings indicate that N is a major factor that negatively affects EI. It is important to mitigate N using thoughtful training, taking into account students’ personalities, to reduce N. In future studies, we will assess how communication trainings for students might enhance EI.
Journal Article
The Drosophila Zinc Finger Transcription Factor Ouija Board Controls Ecdysteroid Biosynthesis through Specific Regulation of spookier
Steroid hormones are crucial for many biological events in multicellular organisms. In insects, the principal steroid hormones are ecdysteroids, which play essential roles in regulating molting and metamorphosis. During larval and pupal development, ecdysteroids are synthesized in the prothoracic gland (PG) from dietary cholesterol via a series of hydroxylation and oxidation steps. The expression of all but one of the known ecdysteroid biosynthetic enzymes is restricted to the PG, but the transcriptional regulatory networks responsible for generating such exquisite tissue-specific regulation is only beginning to be elucidated. Here, we report identification and characterization of the C2H2-type zinc finger transcription factor Ouija board (Ouib) necessary for ecdysteroid production in the PG in the fruit fly Drosophila melanogaster. Expression of ouib is predominantly limited to the PG, and genetic null mutants of ouib result in larval developmental arrest that can be rescued by administrating an active ecdysteroid. Interestingly, ouib mutant animals exhibit a strong reduction in the expression of one ecdysteroid biosynthetic enzyme, spookier. Using a cell culture-based luciferase reporter assay, Ouib protein stimulates transcription of spok by binding to a specific ~15 bp response element in the spok PG enhancer element. Most remarkable, the developmental arrest phenotype of ouib mutants is rescued by over-expression of a functionally-equivalent paralog of spookier. These observations imply that the main biological function of Ouib is to specifically regulate spookier transcription during Drosophila development.
Journal Article
A nonrandomized, single-arm confirmatory trial of expanded endoscopic submucosal dissection indication for undifferentiated early gastric cancer: Japan Clinical Oncology Group study (JCOG1009/1010)
BackgroundWhile endoscopic submucosal dissection (ESD) is recognized as a minimally invasive standard treatment for differentiated early gastric cancers (EGCs), it has not been indicated for undifferentiated EGC (UD-EGC) because of a relatively high risk of lymph node metastasis (LNM). However, patients with surgically resected mucosal (cT1a) UD-EGC ≤ 2 cm in size with no lymphovascular invasion or ulceration are reported to be at a very low risk of LNM. This multicenter, single-arm, confirmatory trial was conducted to evaluate the efficacy and safety of ESD for UD-EGC.MethodsThe key eligibility criteria were endoscopically diagnosed cT1a/N0/M0, single primary lesion, size ≤ 2 cm, no ulceration and histologically proven components of undifferentiated adenocarcinoma on biopsy. Based on the histological findings after ESD, additional gastrectomy was indicated if the criteria for curative resection were not satisfied. The subjects of the primary analysis were patients with UD-EGC as the dominant component. The primary endpoint was 5-year overall survival (OS) of patients with UD-EGC.ResultsThree hundred 46 patients were enrolled from 49 institutions. The proportion of en bloc resection was 99%. No ESD-related Grade 4 adverse events were noted. Delayed bleeding and intraoperative and delayed perforation occurred in 25 (7.3%), 13 (3.8%), and 6 (1.7%) patients, respectively. Among the 275 patients who were the subjects of the primary analysis, curative resection was achieved in 195 patients (71%), and 5-year OS was 99.3% (95% CI: 97.1–99.8).ConclusionsESD can be a curative and less invasive treatment for UD-EGC for patients meeting the eligibility criteria of this study.
Journal Article
Peritoneal Lavage Tumor DNA as a Novel Biomarker for Predicting Peritoneal Recurrence in Pancreatic Ductal Adenocarcinoma
BackgroundThe clinical role of peritoneal lavage cytology (CY) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, partly due to its low sensitivity. This study aimed to develop a new biomarker, defined as peritoneal lavage tumor DNA (ptDNA), using DNAs extracted from peritoneal lavage samples from patients with PDAC.MethodsSamples were collected intraoperatively from 89 PDAC patients who underwent pancreatectomy between 2012 and 2017. Droplet digital polymerase chain reaction (PCR) was used to measure ptDNA for detection of KRAS mutations. The ptDNA status and clinical characteristics were retrospectively evaluated.ResultsPositive ptDNA was found in 41 patients, including all 9 patients positive for CY (CY+) and 32 patients negative for CY (CY−). The mutant allele frequency was significantly higher in the CY+ patients than in the CY− patients. The disease-free survival (DFS) and overall survival (OS) were significantly poorer in the high-ptDNA group than in the low-ptDNA group (median DFS, 11.0 vs. 18.8 months; p = 0.007; median OS, 28.7 vs not reached; p = 0.001). The survival curves of DFS and OS in the CY+ group were almost equal to those in the CY− and high-ptDNA group. In a multivariable analysis, ptDNA was an independent predictive factor for DFS (p = 0.025) and OS (p = 0.047). The estimated cumulative incidence of peritoneal recurrence was 45.5% in the high-ptDNA group. The ptDNA biomarker had a much higher sensitivity for peritoneal recurrence than CY, whereas CY had higher specificity.ConclusionsAs a promising biomarker, ptDNA may predict poor prognosis and peritoneal recurrence in PDAC, resolving the controversy surrounding CY.
Journal Article
Novel pharmacologic inhibition of lysine-specific demethylase 1 as a potential therapeutic for glioblastoma
Lysine-specific demethylase 1 (LSD1/KDM1A) is a pivotal epigenetic enzyme that contributes to several malignancies including malignant glioma. LSD1 is a flavin adenine dinucleotide dependent histone demethylase that specifically targets histone H3 lysine (K) 4 mono- (me1) and di-methylation (me2) and H3K9me1/2 for demethylation. Herein we report the development of an LSD inhibitor, S2172, which efficiently penetrates the blood-brain barrier. S2172 effectively suppresses LSD1 enzymatic activity, resulting in the depletion of cell growth both in vitro in glioma stem cells (GSCs) (mean half-maximal inhibitory concentration (IC50) of 13.8 μM) and in vivo in a GSC orthotopic xenograft mouse model. Treatment with S2172 robustly reduced the expression of the stemness-related genes MYC and Nestin in GSC cells. Consistent with this, chromatin immunoprecipitation-sequencing revealed a significant S2172-dependent alteration in H3K4me2/H3K4me3 status. Furthermore, we identified 284 newly acquired H3K4me2 peak regions after S2172 treatment, which were encompassed within super-enhancer regions. The altered H3K4me2/H3K4me3 status induced by S2172 treatment affected the expression of genes related to tumorigenesis. Our data suggest that targeting LSD1 with S2172 could provide a promising treatment option for glioblastomas, particularly due to targeting of GSC populations.
Journal Article
Clinical impact of monitoring frequency per day as a prospective audit and feedback strategy for patients receiving antimicrobial agents by injection
Background Implementation of antimicrobial stewardship programmes improve antimicrobial therapies and thus result in better patient outcomes and safety. The impact of prospective audit and feedback (PAF) is likely dependent on how frequently it is conducted, and how quickly after antibiotic prescription it is initiated. To our knowledge, however, no report has yet investigated the impact of an increase in monitoring frequency per day on PAF strategy. Here, we evaluated the clinical impact of an increase in monitoring frequency per day as a PAF strategy in patients receiving antimicrobial injections. Methods We conducted a single‐centre, retrospective observational pre‐post study to evaluate the impact of increasing the frequency of monitoring from once daily (once daily review group) to twice daily (twice daily review group). Time to intervention and clinical outcomes were compared before and after implementation of twice daily review. Results Time to intervention for inappropriate antimicrobial therapy was significantly shorter in the twice daily review group than the once daily review group (5.1 ± 6.1 hours vs 29.9 ± 21.5 hours, HR: 4.53, 95% CI: 2.90‐7.07, P < .001). The twice daily review group had a significantly lower rate of clinical failure (16.2% vs 38.3%, P = .004) and hepatotoxicity (4.1% vs 15.0%, P = .035) than the once daily review group. Conclusions An increase in monitoring frequency from once daily to twice daily significantly shortened the time to intervention for inappropriate antimicrobial therapy, with a concomitant reduction in clinical failure and hepatotoxicity.
Journal Article
Cooperative Control of Ecdysone Biosynthesis in Drosophila by Transcription Factors Séance, Ouija Board, and Molting Defective
Ecdysteroids are steroid hormones that control many aspects of development and physiology. During larval development, ecdysone is synthesized in an endocrine organ called the prothoracic gland through a series of ecdysteroidogenic enzymes encoded by the Halloween genes. The expression of the Halloween genes is highly restricted and dynamic, indicating that their spatiotemporal regulation is mediated by their tight transcriptional control. In this study, we report that three zinc finger-associated domain (ZAD)-C2H2 zinc finger transcription factors—Séance (Séan), Ouija board (Ouib), and Molting defective (Mld)—cooperatively control ecdysone biosynthesis in the fruit fly Drosophila melanogaster. Séan and Ouib act in cooperation with Mld to positively regulate the transcription of neverland and spookier, respectively, two Halloween genes. Remarkably, loss-of-function mutations in séan, ouib, or mld can be rescued by the expression of neverland, spookier, or both, respectively. These results suggest that the three transcription factors have distinct roles in coordinating the expression of just two genes in Drosophila. Given that neverland and spookier are located in constitutive heterochromatin, Séan, Ouib, and Mld represent the first example of a transcription factor subset that regulates genes located in constitutive heterochromatin.
Journal Article
The BDNF Val66Met polymorphism affects negative memory bias in civilian women with PTSD
Memory abnormalities are considered a core feature of posttraumatic stress disorder (PTSD). Studies attempting to quantify such memory dysfunction in PTSD have reported that individuals with this disorder exhibit selective memory bias toward negative material. The low expression Met allele of brain-derived neurotrophic factor (
BDNF
) Val66Met polymorphism has been associated with the aetiology of PTSD and with memory abnormalities. It is therefore possible that the
BDNF
Val66Met polymorphism can moderate the relationship between PTSD and memory bias. Here we examined this association in 50 civilian women with PTSD and 70 non-trauma-exposed healthy control women. All subjects were genotyped for the
BDNF
Val66Met (rs6265) polymorphism. Negative memory bias was assessed using a recognition memory task. Patients showed significantly greater negative memory bias compared to controls. In patients, negative memory bias significantly increased with increasing numbers of Met alleles; while no significant relationship was seen in controls. Further pairwise analyses revealed that patients with the Met allele had significantly greater negative memory bias than controls. These results suggest that the relationship between PTSD and negative memory bias can be moderated by the
BDNF
Val66Met polymorphism. More studies are needed to further clarify the relationship between this polymorphism and memory abnormalities in PTSD.
Journal Article
Antimicrobial stewardship intervention for the clinical pathways improves antimicrobial prophylaxis in surgical or non‐surgical invasive therapies
Summary Background The standard duration of administration of antimicrobial prophylaxis in surgery and non‐surgical invasive therapy was shortened according to the promotion of appropriate use. Here, we conducted an intervention to optimise antimicrobial prophylaxis by revising all relevant clinical pathways based on the most recent guidelines. Methods We conducted a single‐centre, prospective cohort study in patients who received antimicrobial prophylaxis to evaluate outcomes following revision of the clinical pathways for antimicrobial prophylaxis. Antibiotic consumption and the duration of antibiotic administration were compared before and after revising the clinical pathways. Results Thirty‐five of 171 clinical pathways were considered inappropriate for antimicrobial use and were optimised. After this revision, the duration of antibiotic administration was significantly shortened (before revision: 3 [1‐5] days vs after revision: 2 [1‐3] days, median [interquartile range], P < 0.001). The rate of discontinuation of antibiotics within 48 h after surgery or non‐surgical invasive therapy was significantly higher after the revision (62.4% vs 81.8%, P < 0.001). In contrast, the incidence of surgical site infection (SSI) was not significantly different before and after the revision (5.7% vs 4.3%, P = 0.177). A multivariate Cox proportional analysis indicated that revision of the clinical pathways was one of the prognostic factors associated with the discontinuation of antibiotics within 48 h after surgery or non‐surgical invasive therapy (hazard ratio, 0.69; 95% confidence interval, 0.63‐0.76, P < 0.001). Conclusions Our findings suggest that revising all relevant clinical pathways was highly effective in reducing antibiotic consumption and shortening the antibiotic administration period without increasing the incidence of SSIs.
Journal Article