Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics

Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC

Recovery from a depressive episode during postgraduate residency training is associated with senior doctors\u27 support

BackgroundDepression among doctors in residency training can have significant impacts on the health of the residents and on patient safety. This study aimed to investigate factors associated with recovery from a depressive episode experienced during postgraduate residency training.MethodsA questionnaire was administered to 2935 first‐year residents at the beginning of residency training in 2011; follow‐up surveys were conducted after 3 months and at the end of the training in 2013. The questionnaire included the Center for Epidemiologic Studies Depression Scale and the Senior Doctor\u27s Support Scale (SDSS). Logistic regression was used to identify associations between factors that may have been related to recovery from depressive episodes.ResultsA total 182 residents experienced a depressive episode in the 3 months after starting residency training. When reassessed at the end of the 2‐year training, 102 (56%) residents had recovered from the episode and 80 (44%) had not. Increased odds of recovery were associated with a middle or high score on the SDSS (middle score odds ratios [OR] 4.45, 95% confidence interval [CI] 1.0‐18.0, P = .04; and high score OR 5.70, 95% CI 1.4‐23.4, P = .02).ConclusionsSupport from senior doctors should be enhanced to optimize recovery from depressive episodes experienced after the start of residency training

Psychiatric-disorder-related behavioral phenotypes and cortical hyperactivity in a mouse model of 3q29 deletion syndrome

3q29 microdeletion, a rare recurrent copy number variant (CNV), greatly confers an increased risk of psychiatric disorders, such as schizophrenia and autism spectrum disorder (ASD), as well as intellectual disability. However, disease-relevant cellular phenotypes of 3q29 deletion syndrome remain to be identified. To reveal the molecular and cellular etiology of 3q29 deletion syndrome, we generated a mouse model of human 3q29 deletion syndrome by chromosome engineering, which achieved construct validity. 3q29 deletion (Df/+) mice showed reduced body weight and brain volume and, more importantly, impaired social interaction and prepulse inhibition. Importantly, the schizophrenia-related impaired prepulse inhibition was reversed by administration of antipsychotics. These findings are reminiscent of the growth defects and neuropsychiatric behavioral phenotypes in patients with 3q29 deletion syndrome and exemplify that the mouse model achieves some part of face validity and predictive validity. Unbiased whole-brain imaging revealed that neuronal hyperactivation after a behavioral task was strikingly exaggerated in a restricted region of the cortex of Df/+ mice. We further elucidated the cellular phenotypes of neuronal hyperactivation and the reduction of parvalbumin expression in the cortex of Df/+ mice. Thus, the 3q29 mouse model provides invaluable insight into the disease-causative molecular and cellular pathology of psychiatric disorders

Head to head comparison of 2D vs real time 3D dipyridamole stress echocardiography

Real-time three-dimensional (RT-3D) echocardiography has entered the clinical practice but true incremental value over standard two-dimensional echocardiography (2D) remains uncertain when applied to stress echo. The aim of the present study is to establish the additional value of RT-3D stress echo over standard 2D stress echocardiography. We evaluated 23 consecutive patients (age = 65 ± 10 years, 16 men) referred for dipyridamole stress echocardiography with Sonos 7500 (Philips Medical Systems, Palo, Alto, CA) equipped with a phased – array 1.6–2.5 MHz probe with second harmonic capability for 2D imaging and a 2–4 MHz matrix-phased array transducer producing 60 × 70 volumetric pyramidal data containing the entire left ventricle for RT-3D imaging. In all patients, images were digitally stored in 2D and 3D for baseline and peak stress with a delay between acquisitions of less than 60 seconds. Wall motion analysis was interpreted on-line for 2D and off-line for RT-3D by joint reading of two expert stress ecocardiographist. Segmental image quality was scored from 1 = excellent to 5 = uninterpretable. Interpretable images were obtained in all patients. Acquisition time for 2D images was 67 ± 21 sec vs 40 ± 22 sec for RT-3D (p = 0.5). Wall motion analysis time was 2.8 ± 0.5 min for 2D and 13 ± 7 min for 3D (p = 0.0001). Segmental image quality score was 1.4 ± 0.5 for 2D and 2.6 ± 0.7 for 3D (p = 0.0001). Positive test results was found in 5/23 patients. 2D and RT-3D were in agreement in 3 out of these 5 positive exams. Overall stress result (positive vs negative) concordance was 91% (Kappa = 0.80) between 2D and RT-3D. During dipyridamole stress echocardiography RT-3D imaging is highly feasible and shows a high concordance rate with standard 2D stress echo. 2D images take longer time to acquire and RT-3D is more time-consuming to analyze. At present, there is no clear clinical advantage justifying routine RT-3D stress echocardiography use

Effects of Mesopore Internal Surfaces on the Structure of Immobilized Pd-Bisphosphine Complexes Analyzed by Variable-Temperature XAFS and Their Catalytic Performances

In this study, mesoporous and nonporous silica-supported Pd complexes were synthesized and characterized. Variable-temperature XAFS measurements and a curve-fitting analysis showed a slightly larger contribution of σ2static when the Pd complexes were on a nonporous support in comparison to a mesoporous support. In contrast, the catalytic performance of the attached Pd complex in the Suzuki-Miyaura cross-coupling reaction was not affected by such small differences in the static disorder of the Pd complex