Introduction : From Fundamentals to Advances in Crowdfunding Research and Practice

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Mapping and Functional Characterisation of a CTCF-Dependent Insulator Element at the 3′ Border of the Murine Scl Transcriptional Domain

The Scl gene encodes a transcription factor essential for haematopoietic development. Scl transcription is regulated by a panel of cis-elements spread over 55 kb with the most distal 3′ element being located downstream of the neighbouring gene Map17, which is co-regulated with Scl in haematopoietic cells. The Scl/Map17 domain is flanked upstream by the ubiquitously expressed Sil gene and downstream by a cluster of Cyp genes active in liver, but the mechanisms responsible for delineating the domain boundaries remain unclear. Here we report identification of a DNaseI hypersensitive site at the 3′ end of the Scl/Map17 domain and 45 kb downstream of the Scl transcription start site. This element is located at the boundary of active and inactive chromatin, does not function as a classical tissue-specific enhancer, binds CTCF and is both necessary and sufficient for insulator function in haematopoietic cells in vitro. Moreover, in a transgenic reporter assay, tissue-specific expression of the Scl promoter in brain was increased by incorporation of 350 bp flanking fragments from the +45 element. Our data suggests that the +45 region functions as a boundary element that separates the Scl/Map17 and Cyp transcriptional domains, and raise the possibility that this element may be useful for improving tissue-specific expression of transgenic constructs

Strategies to prevent intraoperative lung injury during cardiopulmonary bypass

During open heart surgery the influence of a series of factors such as cardiopulmonary bypass (CPB), hypothermia, operation and anaesthesia, as well as medication and transfusion can cause a diffuse trauma in the lungs. This injury leads mostly to a postoperative interstitial pulmonary oedema and abnormal gas exchange. Substantial improvements in all of the above mentioned factors may lead to a better lung function postoperatively. By avoiding CPB, reducing its time, or by minimizing the extracorporeal surface area with the use of miniaturized circuits of CPB, beneficial effects on lung function are reported. In addition, replacement of circuit surface with biocompatible surfaces like heparin-coated, and material-independent sources of blood activation, a better postoperative lung function is observed. Meticulous myocardial protection by using hypothermia and cardioplegia methods during ischemia and reperfusion remain one of the cornerstones of postoperative lung function. The partial restoration of pulmonary artery perfusion during CPB possibly contributes to prevent pulmonary ischemia and lung dysfunction. Using medication such as corticosteroids and aprotinin, which protect the lungs during CPB, and leukocyte depletion filters for operations expected to exceed 90 minutes in CPB-time appear to be protective against the toxic impact of CPB in the lungs. The newer methods of ultrafiltration used to scavenge pro-inflammatory factors seem to be protective for the lung function. In a similar way, reducing the use of cardiotomy suction device, as well as the contact-time between free blood and pericardium, it is expected that the postoperative lung function will be improved

PET Imaging of Microglia Activation and Infection in Neuropsychiatric Disorders with Potential Infectious Origin

The central nervous system (CNS) is an immunoprivileged location for the possible sequestration of latent infections. The presence of pathogens may be involved in the etiology of neuropsychiatric diseases by inducing classical inflammatory responses, hypersensitivity, cellular toxicity, or direct alteration of cellular processes. Infection, persistence, and activation of microbes in the brain are not easy to assess in vivo, and the relation with clinical disease is very difficult to prove. An elegant way to determine an inflammatory response in the brain in vivo is by molecular imaging of microglia activation with [11C]PK11195 and other radiopharmaceuticals that target the translocator protein (TSPO). In this chapter, we summarize the neuroimaging studies that target the TSPO in patients with neuropsychiatric diseases, and we propose positron emission tomography (PET) imaging with radiopharmaceuticals that target the metabolism of infectious agents directly.</p

Cluster randomized trial of a multilevel evidence-based quality improvement approach to tailoring VA Patient Aligned Care Teams to the needs of women Veterans

BACKGROUND: The Veterans Health Administration (VA) has undertaken a major initiative to transform care through implementation of Patient Aligned Care Teams (PACTs). Based on the patient-centered medical home (PCMH) concept, PACT aims to improve access, continuity, coordination, and comprehensiveness using team-based care that is patient-driven and patient-centered. However, how VA should adapt PACT to meet the needs of special populations, such as women Veterans (WVs), was not considered in initial implementation guidance. WVs’ numerical minority in VA healthcare settings (approximately 7–8 % of users) creates logistical challenges to delivering gender-sensitive comprehensive care. The main goal of this study is to test an evidence-based quality improvement approach (EBQI) to tailoring PACT to meet the needs of WVs, incorporating comprehensive primary care services and gender-specific care in gender-sensitive environments, thereby accelerating achievement of PACT tenets for women (Women’s Health (WH)-PACT). METHODS/DESIGN: EBQI is a systematic approach to developing a multilevel research-clinical partnership that engages senior organizational leaders and local quality improvement (QI) teams in adapting and implementing new care models in the context of prior evidence and local practice conditions, with researchers providing technical support, formative feedback, and practice facilitation. In a 12-site cluster randomized trial, we will evaluate WH-PACT model achievement using patient, provider, staff, and practice surveys, in addition to analyses of secondary administrative and chart-based data. We will explore impacts of receipt of WH-PACT care on quality of chronic disease care and prevention, health status, patient satisfaction and experience of care, provider experience, utilization, and costs. Using mixed methods, we will assess pre-post practice contexts; document EBQI activities undertaken in participating facilities and their relationship to provider/staff and team actions/attitudes; document WH-PACT implementation; and examine barriers/facilitators to EBQI-supported WH-PACT implementation through a combination of semi-structured interviews and monthly formative progress narratives and administrative data. DISCUSSION: Lack of gender-sensitive comprehensive care has demonstrated consequences for the technical quality and ratings of care among WVs and may contribute to decisions to continue use or seek care elsewhere under the US Affordable Care Act. We hypothesize that tailoring PACT implementation through EBQI may improve the experience and quality of care at many levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0203985