Objectives: The long-term cardiopulmonary outcomes following preterm birth during the surfactant era remain unclear. Respiratory symptoms, particularly exertional symptoms, are common in preterm children. Therefore, cardiopulmonary exercise testing may provide insights into the pathophysiology driving exertional respiratory symptoms in those born preterm.
View Article and Find Full Text PDFIntroduction: The progression of pulmonary contusions remains poorly understood. This study aimed to measure the radiographic change in pulmonary contusions over time and evaluate the association of the radiographic change with clinical outcomes and surgical stabilization of rib fractures (SSRF).
Methods: This retrospective cohort study included adults admitted with three or more displaced rib fractures or flail segment on trauma CT and when a chest CT was repeated within one week after trauma.
Introduction: The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes.
View Article and Find Full Text PDFBackground: Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population.
Methods: PICSI was a randomised, double-blind, placebo-controlled trial at Perth Children's Hospital (Perth, WA, Australia) to assess whether fluticasone propionate, an inhaled corticosteroid, improves lung function in children who had been born very preterm (<32 weeks of gestation).
Once established within a water resource, harmful algal blooms (HABs) can occur seasonally with an intense and rapid onset, giving water resource managers limited time to respond to lessen risks. An attractive strategy to decrease human, ecological, and economic risks from HABs is to implement proactive algaecide treatments applied to overwintering cyanobacteria (i.e.
View Article and Find Full Text PDFRationale: The respiratory outcomes for adult survivors of preterm birth in the postsurfactant era are wide-ranging with prognostic factors, especially those encountered after the neonatal period, poorly understood.
Objectives: To obtain comprehensive 'peak' lung health data from survivors of very preterm birth and identify neonatal and life-course risk factors for poorer respiratory outcomes in adulthood.
Methods: 127 participants born ≤32 weeks gestation (64%, n=81 with bronchopulmonary dysplasia (BPD), initially recruited according to a 2 with-BPD:1 without-BPD strategy), and 41 term-born controls completed a lung health assessment at 16-23 years, including lung function, imaging and symptom review.
Introduction: The feasibility of prioritizing surgical stabilization of rib fractures (SSRF) in patients with other injuries is unknown. The purpose of this study was to evaluate the timing and outcomes of SSRF between patients with and without non-urgent operative pelvic injuries.
Patients And Methods: In this retrospective observational study, all patients between 2010 and 2020 who underwent SSRF (SSRF group) and those who underwent SSRF and non-urgent operative management of pelvic fractures (SSRF + P group) were included.
J Trauma Acute Care Surg
December 2022
Background: Pulmonary contusion has been considered a contraindication to surgical stabilization of rib fractures (SSRFs). This study aimed to evaluate the association between pulmonary contusion severity and outcomes after SSRF. We hypothesized that outcomes would be worse in patients who undergo SSRF compared with nonoperative management, in presence of varying severity of pulmonary contusions.
View Article and Find Full Text PDFThis review reports on methods used to evaluate airway clearance techniques (ACT) in adults with CF and examined data for evidence of any effect. Sixty-eight studies described ACT in adequate detail and were included in this review. Frequently reported outcomes were sputum expectoration (72%) and spirometric lung function (60%).
View Article and Find Full Text PDFNearly all motile cilia contain a central apparatus (CA) composed of two connected singlet microtubules with attached projections that play crucial roles in regulating ciliary motility. Defects in CA assembly usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of the CA projections are largely unknown.
View Article and Find Full Text PDFWe previously demonstrated that PACRG plays a role in regulating dynein-driven microtubule sliding in motile cilia. To expand our understanding of the role of PACRG in ciliary assembly and motility, we used a combination of functional and structural studies, including newly identified mutants. Using cryo-electron tomography we show that PACRG and FAP20 form the inner junction between the A- and B-tubule along the length of all nine ciliary doublet microtubules.
View Article and Find Full Text PDFThe complex waveforms characteristic of motile eukaryotic cilia and flagella are produced by the temporally and spatially regulated action of multiple dynein subforms generating sliding between subsets of axonemal microtubules. Multiple protein complexes have been identified that are associated with the doublet microtubules and that mediate regulatory signals between key axonemal structures, such as the radial spokes and central apparatus, and the dynein arm motors; these complexes include the N-DRC, MIA, and CSC complexes. Previous studies have shown that PACRG (parkin co-regulated gene) forms a complex that is anchored to the axonemal doublet microtubules.
View Article and Find Full Text PDFCold Spring Harb Perspect Biol
February 2017
Radial spokes are conserved macromolecular complexes that are essential for ciliary motility. A triplet of three radial spokes, RS1, RS2, and RS3, repeats every 96 nm along the doublet microtubules. Each spoke has a distinct base that docks to the doublet and is linked to different inner dynein arms.
View Article and Find Full Text PDFThe use of a thermochemical grafting approach provides a versatile means to functionalise as-synthesised, bulk multi-walled carbon nanotubes (MWNTs) without altering their inherent structure. The associated retention of properties is desirable for a wide range of commercial applications, including for drug delivery and medical purposes; it is also pertinent to studies of intrinsic toxicology. A systematic series of water-compatible MWNTs, with diameter around 12 nm have been prepared, to provide structurally-equivalent samples predominantly stabilised by anionic, cationic, or non-ionic groups.
View Article and Find Full Text PDFBackground: During the assembly and maintenance of cilia, precursor proteins need to be transported from the cell body into the organelle. Intraflagellar transport (IFT) is assumed to be the predominant protein transport pathway in cilia, but it remains largely unknown how ciliary proteins use IFT to reach their destination sites in the cilium and whether the amount of cargo transported by IFT is regulated.
Results: Single-particle imaging showed that DRC4, a structural protein of the axoneme, moves in association with IFT particles inside Chlamydomonas reinhardtii cilia.
Methods Enzymol
August 2013
The axonemal microtubules of cilia/flagella act as a scaffold for assembly of the protein complexes that ultimately regulate dynein activity to control the size and shape of ciliary bends. Despite our general understanding of the contribution of microtubule sliding to ciliary and flagellar motility, many questions regarding the regulation of dynein remain unanswered. For example, we know that the second messenger calcium plays an important role in modulating dynein activity in response to extracellular cues, but it remains unclear how calcium-binding proteins anchored to the axoneme contribute to this regulation.
View Article and Find Full Text PDFMotile cilia and flagella are highly conserved organelles that play important roles in human health and development. We recently discovered a calmodulin- and spoke-associ-ated complex (CSC) that is required for wild-type motility and for the stable assembly of a subset of radial spokes. Using cryo-electron tomography, we present the first structure-based localization model of the CSC.
View Article and Find Full Text PDFVirtually all motile eukaryotic cilia and flagella have a '9+2' axoneme in which nine doublet microtubules surround two singlet microtubules. Associated with the central pair of microtubules are protein complexes that form at least seven biochemically and structurally distinct central pair projections. Analysis of mutants lacking specific projections has indicated that each may play a unique role in the control of flagellar motility.
View Article and Find Full Text PDFFor all eukaryotic cilia the basal bodies provide a template for the assembly of the doublet microtubules, and intraflagellar transport provides a mechanism for transport of axonemal components into the growing cilium. What is not known is how the central pair of microtubules is nucleated or how their associated polypeptides are assembled. Here we report that the Chlamydomonas pf19 mutation results in a single amino acid change within the p60 catalytic subunit of katanin, and that this mutation prevents microtubule severing activity.
View Article and Find Full Text PDFNumerous studies have indicated that each of the seven projections associated with the central pair of microtubules plays a distinct role in regulating eukaryotic ciliary/flagellar motility. Mutants which lack specific projections have distinct motility phenotypes. For example, Chlamydomonas pf6 mutants lack the C1a projection and have twitchy, non-beating flagella.
View Article and Find Full Text PDFGenerating the complex waveforms characteristic of beating cilia requires the coordinated activity of multiple dynein isoforms anchored to the axoneme. We previously identified a complex associated with the C1d projection of the central apparatus that includes primary ciliary dyskinesia protein 1 (Pcdp1). Reduced expression of complex members results in severe motility defects, indicating that C1d is essential for wild-type ciliary beating.
View Article and Find Full Text PDFThe ubiquitous calcium binding protein, calmodulin (CaM), plays a major role in regulating the motility of all eukaryotic cilia and flagella. We previously identified a CaM and Spoke associated Complex (CSC) and provided evidence that this complex mediates regulatory signals between the radial spokes and dynein arms. We have now used an artificial microRNA (amiRNA) approach to reduce expression of two CSC subunits in Chlamydomonas.
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