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Amebiasis, a disease caused by the parasite Entamoeba histolytica, is estimated to cause millions of infections and at least 55,000 deaths globally each year. With no vaccine currently available, there is an urgent need for an accessible means of stimulating protective mucosal immunity. The objective of this study was to characterize the nasal spray of a novel amebiasis vaccine candidate from a syringe-based liquid atomization device, the Teleflex MAD Nasal™, in both adult and infant nasal airways. Human ergonomic testing was completed to determine realistic actuation parameters. Spray pattern, plume geometry, and droplet size distribution were measured to evaluate reproducibility of free plume characteristics. The Alberta Idealized Nasal Inlet (AINI) and three realistic infant nasal airways were used to determine the in vitro deposition profile in adult and infant airways, respectively. Collectively, in vitro results demonstrated the feasibility of delivering the vaccine candidate to target sites within the nasal airways. Penetration through the nasal airways that could lead to deposition in the lungs was below the limit of quantification for both adult and infant geometries, indicating a low likelihood of adverse events due to lung exposure. These results support continued investigation of intranasal delivery of the synthetic Entamoeba histolytica vaccine.

Objective To evaluate several alternative measures of forced expiratory volume in 1 second percent predicted (FEV 1 %pred) variability as potential predictors of future FEV 1 %pred decline in patients with cystic fibrosis. Study design We included 13 827 patients age ≥6 years from the Epidemiologic Study of Cystic Fibrosis 1994-2002 with ≥4 FEV 1 %pred measurements spanning ≥366 days in both a 2-year baseline period and a 2-year follow-up period. We predicted change from best baseline FEV 1 %pred to best follow-up FEV 1 %pred and change from baseline to best in the second follow-up year by using multivariable regression stratified by 4 lung-disease stages. We assessed 5 measures of variability (some as deviations from the best and some as deviations from the trend line) both alone and after controlling for demographic and clinical factors and for the slope and level of FEV 1 %pred. Results All 5 measures of FEV 1 %pred variability were predictive, but the strongest predictor was median deviation from the best FEV 1 %pred in the baseline period. The contribution to explanatory power (R 2 ) was substantial and exceeded the total contribution of all other factors excluding the FEV 1 %pred rate of decline. Adding the other variability measures provided minimal additional value. Conclusions Median deviation from the best FEV 1 %pred is a simple metric that markedly improves prediction of FEV 1 %pred decline even after the inclusion of demographic and clinical characteristics and the FEV 1 %pred rate of decline. The routine calculation of this variability measure could allow clinicians to better identify patients at risk and therefore in need of increased intervention.

Background: Menopause annually affects 25 million women worldwide, and WHO estimates 1.2 billion women will be postmenopausal by 2030. Symptoms of vasomotor changes resulting in hot flashes and night sweats, dysphonic mood, and sleep disturbances affect quality of life in this aging population. Age- related conditions including cardiovascular disease, depression, osteoporosis, osteoarthritis, dementia, and frailty, are linked to menopause. Conventional oral HRT results in increased adverse effects and health outcomes as revealed in the WHI, yet animal studies and some epidemiologic data support benefits of HRT. Hypothesis: Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a favorable risk/benefit profile yet comparative effectiveness studies of this treatment model long term are lacking. Methods: Participants were recruited from the community at large. 300 women gave signed consent, and 75 met strict inclusion/exclusion criteria. Each subject was age and ethnicity matched to a control in the family medicine or women’s clinics. Treatment model subjects(n=75) received physiologic sex steroid transdermal therapy including: estrogen, progesterone and androgens, titrated to physiologic reference ranges. Treatment subjects were prohibited from use of lipid lowering or anti-inflammatory drugs. Control subjects (n=75) received usual care including conventional HRT and lipid lowering drugs. Subjects were evaluated at baseline and follow-up at 3 years for comparative effectiveness on biomarkers related to cardiovascular disease, health outcomes, and quality of life measures. Mixed modeling analysis tested for main effects and group by time interactions including relevant covariates. Results: Of the 9 measures, 4 revealed statistically significant interactions between group membership and time. Fasting Glucose, Co-morbidities, Medication use, and Pain displayed patterns of means indicating that the Treatment Model group either improved while the status quo group remained constant, or the Treatment Model group remained constant while the status quo worsened. Triglycerides improved in both groups. No significant group interactions occurred for BMI and blood pressure. Treatment model subjects did not have any adverse events or adverse changes in inflammatory, hemostatic or endometrial measurements, and improvements occurred for: Visual Analog Bodily Pain, Greene Climacteric Scale, Hamilton Anxiety/ Depression Scales. Conclusion: Transdermal physiological sex steroid hormone therapy was not associated with any adverse events or effects over 3 years, and lead to improved health outcomes and favorable changes on some biomarkers of cardiovascular disease, health outcomes, and quality of life indicators as compared to usual care in aging women.