Molecular mechanism of distinct chemokine engagement and functional divergence of the human Duffy antigen receptor.

The Duffy antigen receptor is a seven-transmembrane (7TM) protein expressed primarily at the surface of red blood cells and displays strikingly promiscuous binding to multiple inflammatory and homeostatic chemokines. It serves as the basis of the Duffy blood group system in humans and also acts as the primary attachment site for malarial parasite Plasmodium vivax and pore-forming toxins secreted by Staphylococcus aureus. Here, we comprehensively profile transducer coupling of this receptor, discover potential non-canonical signaling pathways, and determine the cryoelectron microscopy (cryo-EM) structure in complex with the chemokine CCL7.

Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation.

The Melanocortin-4 Receptor (MC4R) plays a pivotal role in energy homeostasis. We used human MC4R mutations associated with an increased or decreased risk of obesity to dissect mechanisms that regulate MC4R function. Most obesity-associated mutations impair trafficking to the plasma membrane (PM), whereas obesity-protecting mutations either accelerate recycling to the PM or decrease internalization, resulting in enhanced signaling.

Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

Background: Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure.

Objective: We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period.

Normothermic extracorporeal human liver perfusion following donation after cardiac death.

Liver transplantation is a major life-saving procedure and donation after cardiac death (DCD) has increased the pool of potential liver donors. However, livers procured after DCD are at increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to protect, evaluate and, in future, transplant DCD livers.

Normothermic extracorporeal perfusion of isolated porcine liver after warm ischaemia: a preliminary report.

Liver transplantation is a major life-saving procedure, and donation after cardiac death (DCD) has increased the pool of potential liver donors. However, DCD livers are at increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to protect, evaluate and, in future, transplant DCD livers.

Equity in health care and institutional trust: a communitarian view.

Communitarianism acknowledges and values, and not just instrumentally, the bonds that unite and identify communities. Communitarians also value community per se. This paper argues that trust is likely to be stronger in communities where these bonds are greater.

Equity, by what measure?

Equity has in many instances been framed around the notion of fairness. But the metric used to determine what is fair leaves some people at a disadvantage because the things that they value are not always taken properly into account. If I value mangoes and you value oranges is a measure of fairness based on how many oranges I seek appropriate? If I am expected to give up my love of mangoes in order to get ahead is that fair? The debate about judging equity - about measuring fairness - needs to find the conceptual and methodological space to allow the voices and claims of the other to be heard.

An alternative approach to resource allocation: weighted capacity to benefit plus MESH infrastructure.

This article outlines an approach to resource allocation in healthcare that embraces the concepts of 'capacity to benefit' and management economic social and human (MESH) infrastructure. Health service jurisdictions differ in terms of their capacities to produce benefits for the people they serve. This is for three reasons: (i) some populations already have relatively good health, so the capacity to benefit further is limited compared with others; (ii) even where the health levels of two populations are similar, one population's health problems can be more amenable to health service interventions, i.