In Gram-negative bacteria, lipid asymmetry is critical for the function of the outer membrane (OM) as a selective permeability barrier, but how it is established and maintained is poorly understood. Here, we characterize a non-canonical ATP-binding cassette (ABC) transporter in Escherichia coli that provides energy for maintaining OM lipid asymmetry via the transport of aberrantly localized phospholipids (PLs) from the OM to the inner membrane (IM). We establish that the transporter comprises canonical components, MlaF and MlaE, and auxiliary proteins, MlaD and MlaB, of previously unknown functions. We further demonstrate that MlaD forms extremely stable hexamers within the complex, functions in substrate binding with strong affinity for PLs, and modulates ATP hydrolytic activity. In addition, MlaB plays critical roles in both the assembly and activity of the transporter. Our work provides mechanistic insights into how the MlaFEDB complex participates in ensuring active retrograde PL transport to maintain OM lipid asymmetry.DOI: http://dx.doi.org/10.7554/eLife.19042.001

Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, represents 1 of the leading causes of cancer deaths in the world with an estimated 21,670 deaths in the United States in 2013. In contrast to other malignancies, there is an array of treatment options for HCC involving several specialties in the multidisciplinary care of the patient. Consequently, vast heterogeneity in management tendencies has been observed. The objective of this report was to review and compare guidelines on the management of HCC from the United States (National Comprehensive Cancer Network), Europe (European Association for the Study of the Liver-European Organization for Research and Treatment of Cancer), and Asia (consensus statement from the 2009 Asian Oncology Summit). By and large, all 3 guidelines are similar, with some variance in surveillance and treatment allocation recommendations because of regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a concrete, high level of evidence. In contrast to other cancers, the geographic differences in tumor biology and resources make it impractical to have a globally universal guideline for all patients with HCC. Recommendations from the 3 groups are influenced by geographic differences in the prevalence and biology of the disease (ie, areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, finances, and accessibility to treatment). It is important for both physicians and policy makers to include these considerations when treating patients with HCC as well when structuring policies and guidelines.

The addition of a falciform ligament patch and fibrin glue to standard stapled or sutured remnant closure did not reduce the rate or severity of pancreatic fistula in patients undergoing distal pancreatectomy (ClinicalTrials.gov NCT00889213).

The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes.