Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction.

The activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We aimed to study the ability of 3K3A-APC to induce regression of CNV and evaluate vascular endothelial growth factor (VEGF) role in APC's activities in the retina. CNV was induced by laser photocoagulation on C57BL/6J mice. APC and 3K3A-APC were injected intravitreally after verification of CNV presence. CNV volume and vascular penetration were evaluated on retinal pigmented epithelium (RPE)-choroid flatmount by fluorescein isothiocyanate (FITC)-dextran imaging. VEGF levels were measured using immunofluorescence anti-VEGF staining. We found that 3K3A-APC induced regression of pre-existing CNV. VEGF levels, measured in the CNV lesion sites, significantly decreased upon APC and 3K3A-APC treatment. Reduction in VEGF was sustained 14 days post a single APC injection. As 3K3A-APC retained APCs' activities, we conclude that the anticoagulant properties of APC are not mandatory for APC activities in the retina and that VEGF reduction may contribute to the protective effects of APC and 3K3A-APC. Our results highlight the potential use of 3K3A-APC as a novel treatment for CNV and other ocular pathologies.

Evaluation of a novel training package among frontline maternal, newborn, and child health workers in South Sudan.

OBJECTIVE: To develop, implement, and evaluate an evidence-based Maternal, Newborn, and Child Survival (MNCS) package for frontline health workers (FHWs) in South Sudan. METHODS: A multimodal needs assessment was conducted to develop a best-evidence package comprised of targeted training, pictorial checklists, and reusable equipment and commodities. Implementation utilized a training-of-trainers model. Program effectiveness was assessed through knowledge assessments, objective structured clinical examinations (OSCEs), focus groups, and questionnaires. RESULTS: A total of 72 trainers and 708 FHWs were trained in 7 South Sudan states. Trainer knowledge assessments improved significantly: from 62.7% to 92.0% (P<0.001). Mean FHW scores on maternal OSCEs were 21.1% pre-training, 83.4% post-training, and 61.5% 2-3 months after training (P<0.001). Corresponding mean newborn OSCE scores were 41.6%, 89.8%, and 45.7% (P<0.001). Questionnaires revealed high levels of use, satisfaction, and confidence. FHWs reported an average of 3.0 referrals (range, 0-20) to healthcare facilities during the 2-3 months following training, and 78.3% of FHWs were more likely to refer patients. Seven focus groups showed high satisfaction with trainings, commodities, and checklists, with few barriers. CONCLUSION: The MNCS package has led to improved FHW knowledge, skills, and referral. A novel package of training, checklists, and equipment can be successfully implemented in resource-limited settings and enhance links between community-based providers and healthcare facilities.