MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD

Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Liderança e comunicação: estratégias essenciais para o gerenciamento da assistência de enfermagem no contexto hospitalar Liderazgo y comunicación: estratégias esenciales para la gestión de la asistencia de enfermería en el contexto hospitalario Leadership and communication: essential strategies for the management of nursing care in the hospital context

A liderança e a comunicação são estratégias que possibilitam ao enfermeiro promover a melhoria do gerenciamento da assistência de enfermagem no contexto hospitalar. O presente estudo teve como objetivos relatar um programa de Educação Continuada desenvolvido com enfermeiros de um hospital privado sobre liderança e comunicação e apresentar a aplicação da Liderança Situacional na prática profissional destes profissionais. A técnica dos incidentes críticos foi empregada para a coleta dos dados. Os sujeitos participantes do estudo avaliaram positivamente as contribuições oriundas do programa, constatamos também a viabilidade de aplicação da Liderança Situacional no cotidiano da enfermagem.<br>El liderazgo y la comunicación son estrategias que posibilitan al enfermero promover el mejoramiento de la gestión de la asistencia de enfermería en el contexto hospitalario. El presente estudio tuvo como objetivos relatar un programa de educación continuada desarrollado con enfermeros de un hospital privado sobre liderazgo y comunicación y presentar la aplicación del Liderazgo Situacional en su práctica profesional. La técnica de incidentes críticos fue utilizada para la recolección de datos. Los sujetos participantes del estudio evaluaron positivamente las contribuciones del programa y los autores constataron la viabilidad de la aplicación del Liderazgo Situacional en el cotidiano de enfermería.<br>Leadership and communication are strategies that enable nurses to improve the management of nursing care within the hospital context. The present study aimed at reporting a Continuing Education Program developed by nurses from a private hospital on leadership and communication and to present the application of situational leadership in their professional practice. The technique of critical incidents was applied in data collection. The subjects evaluated positively the contributions of the Program and authors found the viability of the application of situational leadership in nursing daily practice