Hand-Held Tidal Breathing Nasal Nitric Oxide Measurement – A Promising Targeted Case-Finding Tool for the Diagnosis of Primary Ciliary Dyskinesia

Background

Nasal nitric oxide (nNO) measurement is an established first line test in the work-up for primary ciliary dyskinesia (PCD). Tidal breathing nNO (TB-nNO) measurements require minimal cooperation and are potentially useful even in young children. Hand-held NO devices are becoming increasingly widespread for asthma management. Therefore, we chose to assess whether hand-held TB-nNO measurements reliably discriminate between PCD, and Healthy Subjects (HS) and included Cystic Fibrosis (CF) patients as a disease control group known to have intermediate nNO levels.

Methods

In this cross sectional, single centre, single occasion, proof-of-concept study in children and adults with PCD and CF, and in HS we compared feasibility, success rates, discriminatory capacity, repeatability and agreement between a hand-held electrochemical device equipped with a nNO software application sampling at flow rates 2 ml/s or 5 ml/s, and two stationary chemiluminescence devices, applying both tidal breathing and velum closure techniques.

Results

Measurements were done in 16 PCD patients, 21 patients with CF and 20 HS aged between 3.8 and 60.9 years. Hand-held TB-nNO showed high success rate (96.5–100%) vs. velum closure nNO techniques (70.2–89.5%). Hand-held TB-nNO sampling at flow rate 5 ml/s showed equally high discriminative power (PCD vs. HS [p<0.0001] and PCD vs. CF [p<0.0001]) and reaching close to 100% sensitivity and specificity, superior repeatability (CV% = 10%) and equal limits of agreement compared to TB-nNO by stationary devices and even compared to velum closure sampling.

Conclusion

Hand-held TB-nNO discriminates significantly between PCD, CF and HS and shows promising potential as a widespread targeted case-finding tool for PCD, although further studies are warranted before implementation.     

Loss-of-Function GAS8 Mutations Cause Primary Ciliary Dyskinesia and Disrupt the Nexin-Dynein Regulatory Complex

Multiciliated epithelial cells protect the upper and lower airways from chronic bacterial infections by moving mucus and debris outward. Congenital disorders of ciliary beating, referred to as primary ciliary dyskinesia (PCD), are characterized by deficient mucociliary clearance and severe, recurrent respiratory infections. Numerous genetic defects, most of which can be detected by transmission electron microscopy (TEM), are so far known to cause different abnormalities of the ciliary axoneme. However, some defects are not regularly discernable by TEM because the ciliary architecture of the axoneme remains preserved. This applies in particular to isolated defects of the nexin links, also known as the nexin-dynein regulatory complex (N-DRC), connecting the peripheral outer microtubular doublets. Immunofluorescence analyses of respiratory cells from PCD-affected individuals detected a N-DRC defect. Genome-wide exome sequence analyses identified recessive loss-of-function mutations in GAS8 encoding DRC4 in three independent PCD-affected families.     

Species accumulation within land use and tree diameter categories in Burkina Faso,Mali, Niger and Senegal

Although farmers have managed west African parkland savanna systems for 1,000 of years, concerns have been raised about the sustainability of these agro-ecosystems due to human population growth, shortening of fallow periods, droughts, desertification and new orientations towards cash generation away from subsistence farming. We conducted a tree diversity survey in 16 villages from Burkina Faso, Mali, Niger and Senegal, recording total species composition for 300 quadrats (mainly 50 × 20 m²) that were randomly sampled from the main landuse categories of parklands of village fields (VF), bush fields (BF), sylvopastoral zone (SP) and forest reserves (FR). About 110 tree species were encountered, including 100 indigenous species. The results from balanced species accumulation curves (based on randomized subsampling of the same number of quadrats from each village) showed that the accumulated number of species was smallest in VF, largest in FR and almost equal in BF and SP, whereas classical (unbalanced) species accumulation curves yielded different results. Although there was a significant within-village reduction in species richness with increasing diameter class [averaging 8.5–13.1 more species in the smallest (<5 cm) compared to the largest diameter class (>80 cm)] for the different landuse categories, new species were also encountered in larger diameter classes (2.7–7.2 species). The evidence for tree regeneration problems (including problems in FR) suggest that farmer-managed tree regeneration should be further explored and that advances in domestication and marketing of indigenous tree species may be crucial to tree conservation in parkland systems.     

New Avian Paramyxoviruses Type I Strains Identified in Africa Provide New Outcomes for Phylogeny Reconstruction and Genotype Classification

Newcastle disease (ND) is one of the most lethal diseases of poultry worldwide. It is caused by an avian paramyxovirus 1 that has high genomic diversity. In the framework of an international surveillance program launched in 2007, several thousand samples from domestic and wild birds in Africa were collected and analyzed. ND viruses (NDV) were detected and isolated in apparently healthy fowls and wild birds. However, two thirds of the isolates collected in this study were classified as virulent strains of NDV based on the molecular analysis of the fusion protein and experimental in vivo challenges with two representative isolates. Phylogenetic analysis based on the F and HN genes showed that isolates recovered from poultry in Mali and Ethiopia form new groups, herein proposed as genotypes XIV and sub-genotype VIf with reference to the new nomenclature described by Diel’s group. In Madagascar, the circulation of NDV strains of genotype XI, originally reported elsewhere, is also confirmed. Full genome sequencing of five African isolates was generated and an extensive phylogeny reconstruction was carried out based on the nucleotide sequences. The evolutionary distances between groups and the specific amino acid signatures of each cluster allowed us to refine the genotype nomenclature.     

Screening clonally replicated Acacia mangium breeding populations for tolerance to Ceratocystis canker and wilt disease

Tree Genetics & Genomes - In forest tree breeding programs, open-pollinated families are frequently used to estimate genetic parameters and evaluate genetic merit of individuals. However, the...