The Hippo pathway noncanonically drives autophagy and cell survival in response to energy stress.

The Hippo pathway is known for its crucial involvement in development, regeneration, organ size control, and cancer. While energy stress is known to activate the Hippo pathway and inhibit its effector YAP, the precise role of the Hippo pathway in energy stress response remains unclear. Here, we report a YAP-independent function of the Hippo pathway in facilitating autophagy and cell survival in response to energy stress, a process mediated by its upstream components MAP4K2 and STRIPAK. Mechanistically, energy stress disrupts the MAP4K2-STRIPAK association, leading to the activation of MAP4K2. Subsequently, MAP4K2 phosphorylates ATG8-family member LC3, thereby facilitating autophagic flux. MAP4K2 is highly expressed in head and neck cancer, and its mediated autophagy is required for head and neck tumor growth in mice. Altogether, our study unveils a noncanonical role of the Hippo pathway in energy stress response, shedding light on this key growth-related pathway in tissue homeostasis and cancer.

Prioritising allocation of donor human breast milk amongst very low birthweight infants in middle-income countries.

The use of donor human breast milk instead of formula reduces the risk of necrotising enterocolitis in preterm infants when their mother's own milk is insufficient. Use of donor milk is limited by the cost of establishing a milk bank and a lack of donors, but the optimal rationing of limited donor milk is unclear. This paper uses an economic model to explore how a limited donor milk supply should be allocated across very low birthweight infants in South Africa considering 2 outcomes: maximising lives saved and minimising costs. We developed a probabilistic cohort Markov decision model with 10,000 infants across 4 birthweight groups. We evaluated allocation scenarios in which infants in each group could be exclusively formula-fed or fed donor milk for 14 or 28 days and thereafter formula until death or discharge. Prioritising infants in the lowest birthweight groups would save the most lives, whereas prioritising infants in the highest birthweight groups would result in the highest cost savings. All allocation scenarios would be considered very cost-effective in South Africa compared to the use of formula; the "worst case" was $619 per Disability Adjusted Life Year averted. There is a compelling argument to increase the supply of donor milk in middle-income countries. Our analysis could be extended by taking a longer term perspective, using data from more than one country and exploring the use of donor milk as an adjunct to mother's own milk, rather than a pure substitute for it.

Cost and Cost-Effectiveness of Donor Human Milk to Prevent Necrotizing Enterocolitis: Systematic Review.

BACKGROUND: Necrotizing enterocolitis (NEC) is a costly gastrointestinal disorder that mainly affects preterm and low-birth-weight infants and can lead to considerable morbidity and mortality. Mother's own milk is protective against NEC but is not always available. In such cases, donor human milk has also been shown to be protective (although to a lesser extent) compared with formula milk, but it is more expensive. This systematic review aimed at evaluating the cost of donor milk, the cost of treating NEC, and the cost-effectiveness of exclusive donor milk versus formula milk feeding to reduce the short-term health and treatment costs of NEC. MATERIALS AND METHODS: We systematically searched five relevant databases to find studies with verifiable costs or charges of donor milk and/or treatment of NEC and any economic evaluations comparing exclusive donor milk with exclusive formula milk feeding. All search results were double screened. RESULTS: Seven studies with verifiable donor milk costs and 17 with verifiable NEC treatment costs were included. The types of cost or charge included varied considerably across studies, so quantitative synthesis was not attempted. Estimates of the incremental length of stay associated with NEC were ∼18 days for medical NEC and 50 days for surgical NEC. Two studies claimed to report economic evaluations but did not do so in practice. CONCLUSIONS: It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC. Future studies should provide more details on cost components included and a full economic evaluation, including long-term outcomes, should be undertaken.