High-energy Femoral Neck Fractures in Young Patients.

Femoral neck fractures in physiologically young patients typically occur from high-energy axial loading forces through the thigh with the hip in an abducted position. These fractures have a high rate of associated head, chest, abdominal, and musculoskeletal injuries. High-energy hip fractures differ from traditional geriatric hip fractures regarding incidence, mechanism, management algorithms, and complications. After adequate resuscitation, goals of treatment include anatomic reduction and stable fixation while maintaining vascularity of the femoral head, which can be achieved through a variety of different techniques. Prompt recognition and treatment of these fractures is crucial to achieve a successful outcome because these injuries are often associated with complications such as osteonecrosis, fixation failure, and nonunion.

A human obesity-associated MC4R mutation with defective Gq/11α signaling leads to hyperphagia in mice.

Melanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity and are associated with hyperphagia and increased linear growth. While MC4R is known to activate Gsα/cAMP signaling, a substantial proportion of obesity-associated MC4R mutations do not affect MC4R/Gsα signaling. To further explore the role of specific MC4R signaling pathways in the regulation of energy balance, we examined the signaling properties of one such mutant, MC4R (F51L), as well as the metabolic consequences of MC4RF51L mutation in mice. The MC4RF51L mutation produced a specific defect in MC4R/Gq/11α signaling and led to obesity, hyperphagia, and increased linear growth in mice. The ability of a melanocortin agonist to acutely inhibit food intake when delivered to the paraventricular nucleus (PVN) was lost in MC4RF51L mice, as well as in WT mice in which a specific Gq/11α inhibitor was delivered to the PVN; this provided evidence that a Gsα-independent signaling pathway, namely Gq/11α, significantly contributes to the actions of MC4R on food intake and linear growth. These results suggest that a biased MC4R agonist that primarily activates Gq/11α may be a potential agent to treat obesity with limited untoward cardiovascular and other side effects.