Whole-exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow-up of a large family.

Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We utilized whole-exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mutant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow-up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia.

Actions of the International Union of Soil Science towards a global agenda for the sustainable use of soils

In a multi-level stakeholder approach the international level is of primordial importance not only in terms of legal frameworks, but also in terms of scientific analysis of the needs, options and constraints, as well as related to monitoring and evaluation systems. The Working Group on 'International Actions for the Sustainable Use of Soils' (IASUS) of the International Union of Soil Science (IUSS) identified a number of issues and measures in preparation of the 17thWorld Congress of Soil Science held in Bangkok, Thailand, in August 2002, and prepared a resolution in support of a 'global agenda for the sustainable use of soils', which was adopted on 21st August 2002 on the closing day of the congress.

EACTS expert consensus statement for surgical management of pleural empyema

Pleural infection is a frequent clinical condition. Prompt treatment has been shown to reduce hospital costs, morbidity and mortality. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research. The European Association for Cardio-Thoracic Surgery (EACTS) Thoracic Domain and the EACTS Pleural Diseases Working Group established a team of thoracic surgeons to produce a comprehensive review of available scientific evidence with the aim to cover all aspects of surgical practice related to its treatment, in particular focusing on: surgical treatment of empyema in adults; surgical treatment of empyema in children; and surgical treatment of post-pneumonectomy empyema (PPE). In the management of Stage 1 empyema, prompt pleural space chest tube drainage is required. In patients with Stage 2 or 3 empyema who are fit enough to undergo an operative procedure, there is a demonstrated benefit of surgical debridement or decortication [possibly by video-assisted thoracoscopic surgery (VATS)] over tube thoracostomy alone in terms of treatment success and reduction in hospital stay. In children, a primary operative approach is an effective management strategy, associated with a lower mortality rate and a reduction of tube thoracostomy duration, length of antibiotic therapy, reintervention rate and hospital stay. Intrapleural fibrinolytic therapy is a reasonable alternative to primary operative management. Uncomplicated PPE [without bronchopleural fistula (BPF)] can be effectively managed with minimally invasive techniques, including fenestration, pleural space irrigation and VATS debridement. PPE associated with BPF can be effectively managed with individualized open surgical techniques, including direct repair, myoplastic and thoracoplastic techniques. Intrathoracic vacuum-assisted closure may be considered as an adjunct to the standard treatment. The current literature cements the role of VATS in the management of pleural empyema, even if the choice of surgical approach relies on the individual surgeon's preference.

The evidence from systematic reviews and meta-analyses published in orthodontic literature. Where do we stand?

AIM To analyse meta-analyses included in systematic reviews (SRs) published in leading orthodontic journals and the Cochrane Database of Systematic Reviews (CDSR) focusing on orthodontic literature and to assess the quality of the existing evidence. MATERIALS AND METHODS Electronic searching was undertaken to identify SRs published in five major orthodontic journals and the CDSR between January 2000 and June 2014. Quality assessment of the overall body of evidence from meta-analyses was conducted using the Grading of Recommendations Assessment, Development and Evaluation working group (GRADE) tool. RESULTS One hundred and fifty-seven SRs were identified; meta-analysis was present in 43 of these (27.4 per cent). The highest proportion of SRs that included a meta-analysis was found in Orthodontics and Craniofacial Research (6/13; 46.1 per cent), followed by the CDSR (12/33; 36.4 per cent) and the American Journal of Orthodontics and Dentofacial Orthopaedics (15/44; 34.1 per cent). Class II treatment was the most commonly addressed topic within SRs in orthodontics (n = 18/157; 11.5 per cent). The number of trials combined to produce a summary estimate was small for most meta-analyses with a median of 4 (range: 2-52). Only 21 per cent (n = 9) of included meta-analyses were considered to have a high/moderate quality of evidence according to GRADE, while the majority were of low or very low quality (n = 34; 79.0 per cent). CONCLUSIONS Overall, approximately one quarter of orthodontic SRs included quantitative synthesis, with a median of four trials per meta-analysis. The overall quality of evidence from the selected orthodontic SRs was predominantly low to very low indicating the relative lack of high quality of evidence from SRs to inform clinical practice guidelines.

[Influence of the pelvic trauma registry of the DGU on treatment of pelvic ring fractures].

Fractures of the pelvic ring are comparatively rare with an incidence of 2-8 % of all fractures depending on the study in question. The severity of pelvic ring fractures can be very different ranging from simple and mostly "harmless" type A fractures up to life-threatening complex type C fractures. Although it was previously postulated that high-energy trauma was necessary to induce a pelvic ring fracture, over the past decades it became more and more evident, not least from data in the pelvic trauma registry of the German Society for Trauma Surgery (DGU), that low-energy minor trauma can also cause pelvic ring fractures of osteoporotic bone and in a rapidly increasing population of geriatric patients insufficiency fractures of the pelvic ring are nowadays observed with no preceding trauma.Even in large trauma centers the number of patients with pelvic ring fractures is mostly insufficient to perform valid and sufficiently powerful monocentric studies on epidemiological, diagnostic or therapeutic issues. For this reason, in 1991 the first and still the only registry worldwide for the documentation and evaluation of pelvic ring fractures was introduced by the Working Group Pelvis (AG Becken) of the DGU. Originally, the main objectives of the documentation were epidemiological and diagnostic issues; however, in the course of time it developed into an increasingly expanding dataset with comprehensive parameters on injury patterns, operative and conservative therapy regimens and short-term and long-term outcome of patients. Originally starting with 10 institutions, in the meantime more than 30 hospitals in Germany and other European countries participate in the documentation of data. In the third phase of the registry alone, which was started in 2004, data from approximately 15,000 patients with pelvic ring and acetabular fractures were documented. In addition to the scientific impact of the pelvic trauma registry, which is reflected in the numerous national and international publications, the dramatically changing epidemiology of pelvic ring fractures, further developments in diagnostics and the changes in operative procedures over time could be demonstrated. Last but not least the now well-established diagnostic and therapeutic algorithms for pelvic ring fractures, which could be derived from the information collated in registry studies, reflect the clinical impact of the registry.