CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.     

Conserved and divergent expression patterns of markers of axial development in the laboratory opossum,Monodelphis domestica

Background: Previous comparative studies suggest that the requirement for Nodal in epiblast and hypoblast development is unique to mammalians. Expression of anterior visceral endoderm (AVE) genes in the visceral endoderm and of their orthologs in the hypoblast may be unique to mammalians and avians, and is absent in the reptilian hypoblast. Axis formation in reptiles is signaled by the formation of the posterior marginal epiblast (PME), which expresses a series of primitive streak genes. To assess the phylogenetic origin of Nodal and AVE gene expression and axis formation in amniotes, we examined marker gene expression in gray short‐tailed opossum, a metatherian. Results: Nodal was expressed in neither epiblast nor hypoblast of opossum embryos. No AVE genes were expressed in the opossum hypoblast. Attainment of polarity in the embryonic disk was signaled by Nodal, Wnt3a, Fgf8, and Bra expression in the PME at 8.5 days post‐coitus. Conclusions: Nodal expression in epiblast or hypoblast may be unique to eutherians. AVE gene expression in visceral endoderm and hypoblast may have been independently acquired in eutherian and avian lineages. PME formation appears to be the event that signals axis formation in reptilian and metatherian embryos, and thus may be an ancestral characteristic of basal amniotes. Developmental Dynamics 245:1176–1188, 2016. © 2016 Wiley Periodicals, Inc.     

Nursing practice environment,quality of care,and morale of hospital nurses in Japan

The purpose of this study was to describe Japanese hospital nurses' perceptions of the nursing practice environment and examine its association with nurse‐reported ability to provide quality nursing care, quality of patient care, and ward morale. A cross‐sectional survey design was used including 223 nurses working in 12 acute inpatient wards in a large Japanese teaching hospital. Nurses rated their work environment favorably overall using the Japanese version of the Practice Environment Scale of the Nursing Work Index. Subscale scores indicated high perceptions of physician relations and quality of nursing management, but lower scores for staffing and resources. Ward nurse managers generally rated the practice environment more positively than staff nurses except for staffing and resources. Regression analyses found the practice environment was a significant predictor of quality of patient care and ward morale, whereas perceived ability to provide quality nursing care was most strongly associated with years of clinical experience. These findings support interventions to improve the nursing practice environment, particularly staffing and resource adequacy, to enhance quality of care and ward morale in Japan.     

Idiopathic sustained left ventricular tachycardia: clinical and electrophysiologic characteristics

Electrophysiologic studies were performed in 16 patients 11 to 45 years old (mean 33 years) with idiopathic sustained (lasting more than 5 min) ventricular tachycardia (VT) originating from the left ventricle. Endocardial mapping during VT showed that the earliest site of activation was at the apical inferior portion of the left ventricle in 14 patients whose QRS morphology during VT showed a right bundle branch block pattern and left-axis deviation, but at the apical anterosuperior portion of the left ventricle in two patients whose QRS morphology during VT showed a right bundle branch block and right-axis deviation. Single programmed ventricular stimulation induced VT in 13 patients, and rapid ventricular pacing induced VT in the remaining three patients. Rapid ventricular pacing terminated VT in all patients. The relationship between the coupling interval and the echo interval was inverse in all eight patients with a wide VT inducible zone. Entrainment was recognized in three of six patients. The initiation of VT by constant pacing depended on the number of pacing beats but not the duration of pacing in all four patients tested. Intravenous verapamil terminated the VT in 13 of 14 patients. Long-term oral verapamil was also effective in all five patients who required long-term oral therapy for their symptoms associated with VT. In conclusion (1) idiopathic left ventricular tachycardia has unique electrocardiographic, electrophysiologic, and electropharmacological properties, (2) the electrophysiologic characteristics suggest that the mechanism is reentry, and (3) verapamil is effective in both the short- and long-term treatment of VT.     

Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic therapy: newly developed bleeding prediction application software,SAMURAI model

Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy.     

Errors reading the Ishihara pseudoisochromatic plates made by observers with normal colour vision

Background: Ishihara pseudoisochromatic plates are one of the best screening tools for red‐green colour vision deficiencies. Although a majority of persons with normal colour vision read all plates correctly, a significant proportion makes mistakes. The purpose of this study was to obtain results for normal trichromats reading the Ishihara plates and analyse the misreading responses to seek clinical implications. Methods: A sample of 249 (161 female) was tested with the Ishihara pseudoisochromatic plates. The number and nature of errors were recorded and typical errors, those that observers with abnormal colour vision were expected to make, were distinguished from other kinds of error. Results: Out of 249 normal trichromats, 111 individuals (45 per cent) misread at least one plate. Females made up to six total errors and males up to five total errors. When only typical errors were counted, all the normal trichromats made two or fewer errors. There was no significant gender difference for either total or typical errors. Conclusion: It is suggested that clinicians count only typical errors when administering the Ishihara test. Using a criterion of no more than two typical errors for a diagnosis of normal colour vision could improve the specificity and sensitivity of the test.