Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis

Background Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. Methods Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean ± SD age 35 ± 9 y, FEV1 66 ± 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. Results CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). Conclusion In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF

The node of Ranvier in CNS pathology.

Healthy nodes of Ranvier are crucial for action potential propagation along myelinated axons, both in the central and in the peripheral nervous system. Surprisingly, the node of Ranvier has often been neglected when describing CNS disorders, with most pathologies classified simply as being due to neuronal defects in the grey matter or due to oligodendrocyte damage in the white matter. However, recent studies have highlighted changes that occur in pathological conditions at the node of Ranvier, and at the associated paranodal and juxtaparanodal regions where neurons and myelinating glial cells interact. Lengthening of the node of Ranvier, failure of the electrically resistive seal between the myelin and the axon at the paranode, and retraction of myelin to expose voltage-gated K(+) channels in the juxtaparanode, may contribute to altering the function of myelinated axons in a wide range of diseases, including stroke, spinal cord injury and multiple sclerosis. Here, we review the principles by which the node of Ranvier operates and its molecular structure, and thus explain how defects at the node and paranode contribute to neurological disorders

Measuring the tail of the dog that doesn't bark in the night: the case of the national evaluation of Choose Life (the national strategy and action plan to prevent suicide in Scotland)

Background Learning about the impact of public health policy presents significant challenges for evaluators. These include the nebulous and organic nature of interventions ensuing from policy directives, the tension between long-term goals and short-term interventions, the appropriateness of establishing control groups, and the problems of providing an economic perspective. An example of contemporary policy that has recently been subject to evaluation is the first phase of the innovative Scottish strategy for suicide prevention (Choose Life). Discussion and summary This paper discusses how challenges, such as those above, were made manifest within this programme. After a brief summary of the overarching approach taken to evaluating the first phase of Choose Life, this paper then offers a set of recommendations for policymakers and evaluators on how learning from a second phase might be augmented. These recommendations are likely to have general resonance across a range of policy evaluations as they move from early planning and implementation to more mature phases