Lessons Learned and Legacy of the Stop Transmission of Polio Program.

In 1988, the by the World Health Assembly established the Global Polio Eradication Initiative, which consisted of a partnership among the World Health Organization (WHO), Rotary International, the Centers for Disease Control and Prevention (CDC), and the United Nations Children's Fund. By 2016, the annual incidence of polio had decreased by >99.9%, compared with 1988, and at the time of writing, only 3 countries in which wild poliovirus circulation has never been interrupted remain: Afghanistan, Nigeria, and Pakistan. A key strategy for polio eradication has been the development of a skilled and deployable workforce to implement eradication activities across the globe. In 1999, the Stop Transmission of Polio (STOP) program was developed and initiated by the CDC, in collaboration with the WHO, to train and mobilize additional human resources to provide technical assistance to polio-endemic countries. STOP has also informed the development of other public health workforce capacity to support polio eradication efforts, including national STOP programs. In addition, the program has diversified to address measles and rubella elimination, data management and quality, and strengthening routine immunization programs. This article describes the STOP program and how it has contributed to polio eradication by building global public health workforce capacity.

Bicarbonate disruption of the pulmonary endothelial barrier via activation of endogenous soluble adenylyl cyclase, isoform 10.

It is becoming increasingly apparent that cAMP signals within the pulmonary endothelium are highly compartmentalized, and this compartmentalization is critical to maintaining endothelial barrier integrity. Studies demonstrate that the exogenous soluble bacterial toxin, ExoY, and heterologous expression of the forskolin-stimulated soluble mammalian adenylyl cyclase (AC) chimera, sACI/II, elevate cytosolic cAMP and disrupt the pulmonary microvascular endothelial barrier. The barrier-disruptive effects of cytosolic cAMP generated by exogenous soluble ACs are in contrast to the barrier-protective effects of subplasma membrane cAMP generated by transmembrane AC, which strengthens endothelial barrier integrity. Endogenous soluble AC isoform 10 (AC10 or commonly known as sAC) lacks transmembrane domains and localizes within the cytosolic compartment. AC10 is uniquely activated by bicarbonate to generate cytosolic cAMP, yet its role in regulation of endothelial barrier integrity has not been addressed. Here we demonstrate that, within the pulmonary circulation, AC10 is expressed in pulmonary microvascular endothelial cells (PMVECs) and pulmonary artery endothelial cells (PAECs), yet expression in PAECs is lower. Furthermore, pulmonary endothelial cells selectively express bicarbonate cotransporters. While extracellular bicarbonate generates a phosphodiesterase 4-sensitive cAMP pool in PMVECs, no such cAMP response is detected in PAECs. Finally, addition of extracellular bicarbonate decreases resistance across the PMVEC monolayer and increases the filtration coefficient in the isolated perfused lung above osmolality controls. Collectively, these findings suggest that PMVECs have a bicarbonate-sensitive cytosolic cAMP pool that disrupts endothelial barrier integrity. These studies could provide an alternative mechanism for the controversial effects of bicarbonate correction of acidosis of acute respiratory distress syndrome patients.