Prior research has utilised person-centred approaches to identify parent feeding profiles distinguished by controlling and structure-based practices, but less research has examined autonomy support-ba Show more
Prior research has utilised person-centred approaches to identify parent feeding profiles distinguished by controlling and structure-based practices, but less research has examined autonomy support-based practices, or how social and family contextual factors differ between feeding profiles. This study aimed to identify profiles of parents with similar patterns of feeding practices and to examine whether profiles differ on family contextual factors. In 2022, 989 UK parents of children aged 3-6 years (M = 4.1 years) completed an online survey, which included the Comprehensive Feeding Practices Questionnaire (CFPQ), measuring parental feeding practices, and validated questionnaires capturing family contextual variables. Latent Profile Analysis (LPA) was conducted to identify parent feeding profiles using the CFPQ. A MANCOVA assessed differences in family contextual variables between profiles. LPA identified three profiles based on common model fit indices and theoretical considerations. Profile 1 'moderate control' (25.2%) showed moderate use of controlling practices and low use of structure-based and autonomy support-based practices. Profile 2 'structured and supportive' (29.6%) showed low use of controlling practices and high use of structure-based and autonomy support-based practices. Profile 3 'using everything' (45.2%) showed high use of all three types of feeding practices. Parents in the 'moderate control' profile had significantly lower parental wellbeing and reported more barriers of time and energy for meal planning compared to other profiles. In contrast, parents in the 'structured and supportive' profile had significantly lower household chaos and lower parental stress. Mothers had a higher proportion of membership to the 'structured and supportive' profile (33.9%) compared to other profiles, whereas fathers had a higher membership proportion to the 'using everything' profile (60.9%). Future interventions should be tailored to parent feeding practice profiles and associated family contextual factors. Show less
REV-ERBα has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERBα agonists based on GSK4112 (1 Show more
REV-ERBα has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERBα agonists based on GSK4112 (1) for potency, selectivity, and bioavailability. (1) Potent REV-ERBα agonists 4, 10, 16, and 23 are detailed for their ability to suppress BMAL and IL-6 expression from human cells while also demonstrating excellent selectivity over LXRα. Amine 4 demonstrated in vivo bioavailability after either iv or oral dosing. Show less
The liver X receptors (LXRalpha/beta) are orphan nuclear receptors that are expressed in a large number of cell types and have been shown to have anti-inflammatory properties. Nuclear receptors have p Show more
The liver X receptors (LXRalpha/beta) are orphan nuclear receptors that are expressed in a large number of cell types and have been shown to have anti-inflammatory properties. Nuclear receptors have previously proved to be amenable targets for small molecular mass pharmacological agents in asthma, and so the effect of an LXR ligand was assessed in models of allergic airway inflammation. LXR agonist, GW 3965, was profiled in rat and mouse models of allergic asthma. In the Brown Norway rats, GW 3965 (3-30 mg/kg) was unable to reduce the bronchoalveolar lavage eosinophilia associated with this model and had no impact on inflammatory biomarkers (eotaxin and IL-1beta). The compound did significantly stimulate ABCA-1 (ATP-binding cassette A1) mRNA expression, indicating that there was adequate exposure/LXR activation. In the mouse model, the LXR ligand surprisingly increased airway reactivity, an effect that was apparent in both the Ag and nonchallenged groups. This increase was not associated with a change in lung tissue inflammation or number of mucus-containing cells. There was, however, a marked increase in airway smooth muscle thickness in both treated groups. We demonstrated an increase in contractile response to exogenous methacholine in isolated airways taken from LXR agonist-treated animals compared with the relevant control tissue. We corroborated these findings in a human system by demonstrating increased proliferation of cultured airway smooth muscle. This phenomenon, if evidenced in man, would indicate that LXR ligands may directly increase airway reactivity, which could be detrimental, especially in patients with existing respiratory disease and with already compromised lung function. Show less