Clinical and research priorities for children and young people with bronchiectasis: an international roadmap.

The global burden of children and young people (CYP) with bronchiectasis is being recognised increasingly. They experience a poor quality of life and recurrent respiratory exacerbations requiring additional treatment, including hospitalisation. However, there are no published data on patient-driven clinical needs and/or research priorities for paediatric bronchiectasis. Parent/patient-driven views are required to understand the clinical needs and research priorities to inform changes that benefit CYP with bronchiectasis and reduce their disease burden. The European Lung Foundation and the European Respiratory Society Task Force for paediatric bronchiectasis created an international roadmap of clinical and research priorities to guide, and as an extension of, the clinical practice guideline. This roadmap was based on two global web-based surveys. The first survey (10 languages) was completed by 225 respondents (parents of CYP with bronchiectasis and adults with bronchiectasis diagnosed in childhood) from 21 countries. The parent/patient survey encompassed both clinical and research priorities. The second survey, completed by 258 health practitioners from 54 countries, was limited to research priorities. The two highest clinical needs expressed by parents/patients were: having an action management plan for flare-ups/exacerbations and access to physiotherapists. The two highest health practitioners' research priorities related to eradication of airway pathogens and optimal airway clearance techniques. Based on both surveys, the top 10 research priorities were derived, and unanimous consensus statements were formulated from these priorities. This document addresses parents'/patients' clinical and research priorities from both the parents'/patients' and clinicians' perspectives and will help guide research and clinical efforts to improve the lives of people with bronchiectasis

Evidence for the ‘Good Genes’ Model: Association of MHC Class II DRB Alleles with Ectoparasitism and Reproductive State in the Neotropical Lesser Bulldog Bat, Noctilio albiventris

The adaptive immune system has a major impact on parasite resistance and life history strategies. Immunological defence is costly both in terms of immediate activation and long-term maintenance. The ‘good genes’ model predicts that males with genotypes that promote a good disease resistance have the ability to allocate more resources to reproductive effort which favours the transmission of good alleles into future generations. Our study shows a correlation between immune gene constitution (Major Histocompatibility Complex, MHC class II DRB), ectoparasite loads (ticks and bat flies) and the reproductive state in a neotropical bat, Noctilio albiventris. Infestation rates with ectoparasites were linked to specific Noal-DRB alleles, differed among roosts, increased with body size and co-varied with reproductive state particularly in males. Non-reproductive adult males were more infested with ectoparasites than reproductively active males, and they had more often an allele (Noal-DRB*02) associated with a higher tick infestation than reproductively active males or subadults. We conclude that the individual immune gene constitution affects ectoparasite susceptibility, and contributes to fitness relevant trade-offs in male N. albiventris as suggested by the ‘good genes’ model

A Computational Model of the Ionic Currents, Ca2+ Dynamics and Action Potentials Underlying Contraction of Isolated Uterine Smooth Muscle

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: currents (L- and T-type), current, an hyperpolarization-activated current, three voltage-gated currents, two -activated current, -activated current, non-specific cation current, - exchanger, - pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area∶volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular computed from known fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing . This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels