Andrew J. Malek

Objective: To determine if increased food security (FS) reduces mortality, prevalence, and disability in patients with orofacial clefts (OFCs). Design: Ecological study. Setting: A total of 204 countries and territories in the Global Burden of Disease Study and FS data from 113 countries from the Global Food Security Index. Patients, Participants: Deidentified country-level data on patients with OFCs <4 years old from years 2012 to 2019. Interventions: None. Main Outcome Measure: Number of deaths from OFCs, prevalence of OFCs, and disability adjusted life years (DALYs) from OFCs per 100,000 people. Results: Of 113 countries with data from 2012 to 2019, regression showed a 13.8% decreased rate of death (incidence rate ratio 0.862 [95% confidence interval (CI) 0.852, 0.871]) and 74.9% higher odds of nondeath (odds ratio 1.749 [95% CI 1.106, 2.786]) with a 1-point increase in FS score. A linear relationship was demonstrated between FS and prevalence of OFCs (β −18.5 [95% CI −34.8, −2.3]) and DALYs from OFCs (β −43.1 [95% CI −62.6, −23.5]) with a 1-point increase in FS score as well. The greatest reductions in mortality and DALYs were seen in children <1 year whereas reductions in prevalence were seen in children 2-4 years, attributed to decreases in late presentations. Conclusion: Our study shows higher FS is associated with reduced deaths from OFCs, prevalence of OFCs, and DALYs from OFCs. We hope our study validates efforts by nutritional programs led by OFC teams and provides evidence for further support.

Background: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. Methods and Results: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF‐RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF‐RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF‐RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF‐RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial‐dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1β, and expression of profibrotic mediators. RF‐RDN failed to exert beneficial effects when administered in the 20‐week‐old HFpEF cohort. Conclusions: Our data demonstrate that early RF‐RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF‐RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.