Effects of physical activity and sedentary time on depression, anxiety and well-being: a bidirectional Mendelian randomisation study.

BACKGROUND: Mental health conditions represent one of the major groups of non-transmissible diseases. Physical activity (PA) and sedentary time (ST) have been shown to affect mental health outcomes in opposite directions. In this study, we use accelerometery-derived measures of PA and ST from the UK Biobank (UKB) and depression, anxiety and well-being data from the UKB mental health questionnaire as well as published summary statistics to explore the causal associations between these phenotypes. METHODS: We used MRlap to test if objectively measured PA and ST associate with mental health outcomes using UKB data and summary statistics from published genome-wide association studies. We also tested for bidirectional associations. We performed sex stratified as well as sensitivity analyses. RESULTS: Genetically instrumented higher PA was associated with lower odds of depression (OR = 0.92; 95% CI: 0.88, 0.97) and depression severity (beta = - 0.11; 95% CI: - 0.18, - 0.04), Genetically instrumented higher ST was associated higher odds of anxiety (OR = 2.59; 95% CI: 1.10, 4.60). PA was associated with higher well-being (beta = 0.11, 95% CI: 0.04; 0.18) and ST with lower well-being (beta = - 0.18; 95% CI: - 0.32, - 0.03). Similar findings were observed when stratifying by sex. There was evidence for a bidirectional relationship, with higher genetic liability to depression associated with lower PA (beta = - 0.25, 95% CI: - 0.42; - 0.08) and higher well-being associated with higher PA (beta = 0.15; 95% CI: 0.05, 0.25). CONCLUSIONS: We have demonstrated the bidirectional effects of both PA and ST on a range of mental health outcomes using objectively measured predictors and MR methods for causal inference. Our findings support a causal role for PA and ST in the development of mental health problems and in affecting well-being.

Experimentation with aerosol bonsetan, pirfenidone, treprostinil and sidenafil.

INTRODUCTION: Pulmonary hypertension (PH) has been identified either as a symptom or a primary entity. Several drugs are already on the market and other are being investigated. Idiopathic pulmonary fibrosis (IPF) is also a disease were several drugs are being investigated. MATERIALS AND METHODS: Three jet nebulizers and three ultrasound nebulizers were used for our experiments with seven different residual cups and four different loadings. Bonsetan, treprostinil, sidenafil and pirfenidone were modified in order to be produced as aerosol in an effort to identify parameters which influence the droplet size production size. RESULTS: The four-way ANOVA on droplet size using the jet nebulizers revealed two statistically significant factors, drug (F=6.326, P=0.0007) and residual cup (F=4.419, P=0.0007), and their interaction term (F=5.829, P<0.0001). Drugs bonsetan and pirfenidone produce equally the lowest mean droplet size (2.63 and 2.80 respectively) as compared to other two drug mean sizes. The ANOVA results, concerning the ultrasound nebulizers, revealed only the nebulizers as producing significant effect on droplet size (F=4.753, P=0.037). DISCUSSION: Our study indicates the importance of the initial drug design formulation. Moreover, further investigation of the residual cup design is an additional parameter that can assist in the optimal droplet size production, indifferently of the drug formulation.