BackgroundNew therapies for asthma which can address three main interrelated features of the disease, airway inflammation, airway remodeling and airway hyperreactivity, are urgently required. Resveratrol, a well known red wine polyphenol has received much attention due to its potential anti-aging properties. This compound is an agonist of silent information regulator two histone deacetylases and has many effects that are relevant to key aspects of the pathophysiology of asthma including inflammation, cell proliferation and fibrosis. Therefore, resveratrol may offer a novel asthma therapy that simultaneously inhibits airway inflammation, and airway remodeling which are the main contributors to airway hyperreactivity and irreversible lung function loss.MethodsWe evaluated the effects of systemic resveratrol treatment in a murine model of chronic allergic airways disease which displays most of the clinicopathological features of severe human asthma. Wild-type Balb/c mice with allergic airways disease were treated with 12.5 mg/kg resveratrol or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and histological examination of lung tissue sections. Further, remodeling was assessed by morphometric analysis and lung function was assessed by invasive plethysmography measurement of airway resistance and dynamic compliance.ResultsMice treated with resveratrol exhibited reduced tissue inflammation as compared to vehicle treated mice (p<0.05). Additionally, resveratrol treatment resulted in reduced subepithelial collagen deposition as compared to vehicle treated mice (p<0.05) and attenuated airway hyperreactivity (p<0.05).ConclusionsThese novel findings demonstrate that treatment with resveratrol can reduce structural airway remodeling changes and hyperreactivity. This has important implications for the development of new therapeutic approaches to asthma.

PurposePopulation-based carrier screening for fragile X syndrome (FXS) is still not universally endorsed by professional organizations due to concerns around genetic counseling for complex information and potential for psychosocial harms.MethodsWe determined uptake levels, decision making, and psychosocial impact in a prospective study of pregnant and nonpregnant Australian women offered FXS carrier screening in clinical settings. Women received pretest genetic counseling, and completed questionnaires when deciding and one month later.ResultsOf 1,156 women recruited, 83.1% returned the first questionnaire with 70.6% nonpregnant and 58.8% pregnant women choosing testing (χ=16.98, P<0.001). Overall, informed choice was high in both nonpregnant (77.4%) and pregnant (72.9%) women (χ=0.21, P=0.644), and more tested (76.0%) than not-tested (66.7%) women (χ=6.35, P=0.012) made an informed choice. Measures of depression, stress, and anxiety were similar to population norms for ~85% of women. Decisional conflict and regret were generally low; however, decisional uncertainty and regret were greater in pregnant than nonpregnant women, and not-tested than tested women (uncertainty: χ=18.51, P<0.001 and χ=43.11, P<0.001, respectively; regret: χ=6.61, P<0.037 and χ=35.54, P<0.001, respectively).ConclusionWe provide evidence to inform guidelines that population FXS carrier screening can be implemented with minimal psychosocial harms following appropriate information and prescreening genetic counseling.

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There is a need for new asthma therapies that can concurrently address airway remodeling, airway hyperresponsiveness and progressive irreversible loss of lung function, in addition to inhibiting inflammation. Histone deacetylase inhibitors (HDACi) alter gene expression by interfering with the removal of acetyl groups from histones. The HDACi trichostatin A (TSA) has pleiotropic effects targeting key pathological processes in asthma including inflammation, proliferation, angiogenesis and fibrosis. The aim was to evaluate the effects of TSA treatment in a mouse model of chronic allergic airways disease (AAD). Wild-type BALB/c mice with AAD were treated intraperitoneally with 5 mg/kg TSA or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid (BALF) cell counts and histological examination of lung tissue sections. Remodeling was assessed by morphometric analysis and airway hyperresponsiveness was assessed by invasive plethysmography. TSA-treated mice had a reduced number of total inflammatory cells and eosinophils within the BALF as compared to vehicle-treated mice (both p < 0.05). Furthermore, airway remodeling changes were significantly reduced with TSA compared to vehicle-treated mice, with fewer goblet cells (p < 0.05), less subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness at the highest methacholine dose. These findings demonstrate that treatment with an HDACi can concurrently reduce structural airway remodeling changes and airway hyperresponsiveness, in addition to attenuating airway inflammation in a chronic AAD model. This has important implications for the development of novel treatments for severe asthma.