Computational design of a modular protein sense-response system.

Sensing and responding to signals is a fundamental ability of living systems, but despite substantial progress in the computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here, we describe a generalizable computational strategy for designing sensor-actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation through split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site closely matches the design model. Our computational design strategy opens broad avenues to link biological outputs to new signals.

Report on Implementation, Use, and Sustainability of a Labor Epidural Service in Georgetown, Guyana.

BACKGROUND: The use of epidural analgesia for laboring women is generally unavailable at public hospitals in Guyana despite favorable utilization rates in private institutions. In 2014, a healthcare team completed a targeted mission aimed at neuraxial analgesia training of providers at the preeminent public hospital in Georgetown, Guyana. This study evaluates the impact of the training, including provider attitudes, use, and barriers. METHODS: A prospective, mixed methods study of all obstetric, nursing, and anesthesiology providers at Georgetown Public Hospital Corporation was completed. Quantitative assessment of the posttraining use of epidural analgesia at 2 and 6 months was documented. Provider surveys were distributed anonymously at 2 months posttraining. Targeted interviews were completed from a random sampling of providers at 6 months; qualitative analysis of interviews formulated the basis for reporting limitations and barriers. RESULTS: Providers surveyed included 7 anesthesia providers and 24 obstetrics providers. Respondents believed Guyanese women should be offered epidural analgesia (93%), epidurals could be performed safely (87%), and Guyana has the resources necessary for routine use (81%). In assessing epidural knowledge, anesthesia providers achieved 60% correct response rate compared to 84% among obstetrics providers. Nurse anesthetists placed 16 epidurals following training. However, placement ceased after 2 months. The largest barriers to placement were unavailable anesthesia staff (63%), lack of supplies (16%), and insufficient nursing staff to monitor patients with epidurals (11%). CONCLUSIONS: A 1-week mission achieved widespread Guyanese provider acceptance despite a lack of previous experience. However, barriers proved insurmountable to achieving a sustainable, independently functioning epidural analgesia program.