Cryo-EM analysis of complement C3 reveals a reversible major opening of the macroglobulin ring.

The C3 protein is the central molecule within the complement system and undergoes proteolytic activation to C3b in the presence of pathogens. Pattern-independent activation of C3 also occurs via hydrolysis, resulting in C3(HO), but the structural details of C3 hydrolysis remain elusive. Here we show that the conformation of the C3(HO) analog, C3MA, is indistinguishable from C3b.

Quality Improvement Intervention Decreases Pain and Adverse Events Due to Heel Lances in Infants.

Background: Studies have investigated ways to reduce infants' pain during heel lancing, but research on preventing adverse events is scarce. This study investigated whether or not the number of infants with normal comfort (>8 and ≤14), distress (≤4), and pain (≤4) scores increased and whether or not the number of adverse events (blue and/or edematous heels and improperly placed incisions) decreased during and after heel lancing following an intervention.

Methods: A pre- and post-quality improvement intervention including 189 and 186 heel lances, respectively, in infants (postmenstrual age ≥ 28 + 0 to ≤ 43 + 6 weeks) was conducted in May to July 2020 and April to July 2022.

Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort.

Background: People living with cystic fibrosis in Denmark had early, universal access to triple modulator treatment with elexacaftor/tezacaftor/ivacaftor. Close monitoring allowed us to assess the impact of treatment on lung function and progression of lung disease in an unselected nationwide cystic fibrosis population from 6 years of age.

Methods: Data were analysed using linear mixed-effect models to assess changes in levels and annual rates of change (slopes) in percent predicted (pp) forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF) between the 12 months pre-treatment and treatment periods.

Impact of elexacaftor/tezacaftor/ivacaftor on utilization of routine therapies in cystic fibrosis: Danish nationwide register study.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been effective in improving several outcomes in people living with cystic fibrosis (pwCF). Although clinical guidance regarding maintenance therapies has not changed, staff reports indicate that individuals reduce some therapies. This study aimed to evaluate ETI's effect on utilization of routine therapies among pwCF in Denmark.