Use of exhaled nitric oxide in the diagnosis and monitoring of childhood asthma: myth or maxim?

Asthma is a common condition in children. This review describes the evidence from the literature and international asthma guidelines for using fractional exhaled nitric oxide (FENO) in the diagnosis and monitoring of childhood asthma. The accuracy of FENO measuring devices could be further improved, the difference in FENO results between devices are equivalent to what is considered a clinically important difference. For diagnosing asthma no guideline currently recommends FENO is used as the first test, but many recommend FENO as part of a series of tests. A cut-off of 35 ppb is widely recommended as being supportive of an asthma diagnosis, but evidence from children at risk of asthma suggests that a lower threshold of 25 ppb may be more appropriate. Nine randomised clinical trials including 1885 children have added FENO to usual asthma care and find that exacerbations are reduced when care is guided by FENO (OR for exacerbation compared to usual care 0.77, 95% CI 0.62-0.94). What is not clear is what cut-off(s) of FENO should be used to trigger a change in treatment. After 30 years of intensive research there is not sufficient evidence to recommend FENO for routine diagnosing and monitoring asthma in children. Educational aims: To give the reader an overview of literature that supports and does not support the role of FENO in diagnosing asthma in children.To give the reader an overview of literature that supports and does not support the role of FENO in monitoring asthma in children.To give the reader an understanding of the role of FENO in international guidelines for diagnosing and monitoring asthma in children.

A Sulfonated All-Aromatic Polyamide for Heavy Metal Capture: A Model Study with Pb(II).

Polyelectrolytes are widely used in heavy metal removal, finding applications as coagulants and flocculants. We compare the heavy metal removal capability of a water-soluble sulfonated semirigid polyamide, poly(2,2'-disulfonyl-4,4'-benzidine isophthalamide) (PBDI), with that of a well-known random-coil polymer, poly(sodium 4-styrenesulfonate) (PSS). Using lead (Pb(II)) as a model contaminant, both polymers precipitate out from solution at ~500 mg/L Pb(II) in water. The ability to remove Pb(II) from water was quantified using adsorption isotherms and fitted with Langmuir and Freundlich adsorption models. The sorption of Pb(II) by PSS fit the Langmuir model with a high degree of correlation (0.976 R2), but the sorption of Pb(II) by PBDI could not be accurately predicted using the Langmuir or Freundlich model. The sorption of Pb(II) by PBDI and PSS was compared by normalizing sorption by the number of sulfonate groups of each polymer and the ion exchange capacity (IEC), found by titration. We find that PBDI removes a greater amount of Pb(II) per gram of sorbent compared to PSS, 410 mg/g vs 260 mg/g, respectively, which cannot be accounted for by differences in IEC or number of sulfonate groups. Our findings confirm that the positioning of the sulfonate groups and the rigidity of the polymer backbone play an important role in how Pb(II) coordinates to the polymer prior to precipitating out from solution.

RelB-deficient autoinflammatory pathology presents as interferonopathy, but in mice is interferon-independent.

BACKGROUND: Autoimmune diseases are leading causes of ill health and morbidity and have diverse etiology. Two signaling pathways are key drivers of autoimmune pathology, interferon and nuclear factor-κB (NF-κB)/RelA, defining the 2 broad labels of interferonopathies and relopathies. Prior work has established that genetic loss of function of the NF-κB subunit RelB leads to autoimmune and inflammatory pathology in mice and humans. OBJECTIVE: We sought to characterize RelB-deficient autoimmunity by unbiased profiling of the responses of immune sentinel cells to stimulus and to determine the functional role of dysregulated gene programs in the RelB-deficient pathology. METHODS: Transcriptomic profiling was performed on fibroblasts and dendritic cells derived from patients with RelB deficiency and knockout mice, and transcriptomic responses and pathology were assessed in mice deficient in both RelB and the type I interferon receptor. RESULTS: We found that loss of RelB in patient-derived fibroblasts and mouse myeloid cells results in elevated induction of hundreds of interferon-stimulated genes. Removing hyperexpression of the interferon-stimulated gene program did not ameliorate the autoimmune pathology of RelB knockout mice. Instead, we found that RelB suppresses a different set of inflammatory response genes in a manner that is independent of interferon signaling but associated with NF-κB binding motifs. CONCLUSION: Although transcriptomic profiling would describe RelB-deficient autoimmune disease as an interferonopathy, the genetic evidence indicates that the pathology in mice is interferon-independent.

Linear versus Nonlinear Aromatic Polyamides: The Role of Backbone Geometry in Thin Film Salt Exclusion Membranes.

Two aromatic polyamides─poly(3,3'-dihydroxybenzidine terephthalamide) (DHTA) and poly(3,3'-dihydroxybenzidine isophthalamide) (DHIA)─are compared for their ability to remove salts from water. DHTA is linear and rigid whereas DHIA is nonlinear and semirigid. DHTA and DHIA were selected as they allow us to investigate the effect of polymer backbone geometry on salt exclusion in a non-crosslinked thin film membrane, independently of the backbone chemistry. Because of their differences in solution viscosity, spin coating parameters for DHTA and DHIA solutions were optimized separately to produce thin film composites (TFCs) with reproducible membrane properties. The resulting DHTA TFCs displayed salt rejections of 87.8% (NaCl), 97.0% (MgSO4), and 80.3% (CaCl2). In comparison, DHIA TFCs demonstrated poor salt rejections of 21.0% (NaCl), 29.3% (MgSO4), and 15.4% (CaCl2). Cross-sectional SEM images of DHTA and DHIA films reveal that DHTA has a stratified (layered) morphology whereas DHIA exhibits a dense, featureless morphology. Both DHTA and DHIA TFCs exhibit similar surface morphology, contact angle, surface charge, and water uptake. PEG rejection experiments indicate that the average pore size of DHTA TFCs is ∼2 nm while DHIA TFCs have an average pore size of ∼3 nm. Our findings illustrate that using a rigid, linear aromatic polyamide gives an active layer with a stratified morphology, uniplanar orientation, smaller pores, and higher salt rejection, whereas the nonlinear aromatic polyamide analogue results in an isotropic active layer with larger pores and lower salt rejection.

Characterization of dual specificity protein kinase from maize seedlings.

A protein kinase of 57 kDa, able to phosphorylate tyrosine in synthetic substrates pol(Glu4,Tyr1) and a fragment of Src tyrosine kinase, was isolated and partly purified from maize seedlings (Zea mays). The protein kinase was able to phosphorylate exogenous proteins: enolase, caseins, histones and myelin basic protein. Amino acid analysis of phosphorylated casein and enolase, as well as of phosphorylated endogenous proteins, showed that both Tyr and Ser residues were phosphorylated. Phosphotyrosine was also immunodetected in the 57 kDa protein fraction. In the protein fraction there are present 57 kDa protein kinase and enolase. This co-purification suggests that enolase can be an endogenous substrate of the kinase. The two proteins could be resolved by two-dimensional electrophoresis. Specific inhibitors of typical protein-tyrosine kinases had essentially no effect on the activity of the maize enzyme. Staurosporine, a nonspecific inhibitor of protein kinases, effectively inhibited the 57 kDa protein kinase. Also, poly L-lysine and heparin inhibited tyrosine phosphorylation by 57 kDa maize protein kinase. The substrate and inhibitor specificities of the 57 kDa maize protein kinase phosphorylating tyrosine indicate that it is a novel plant dual-specificity protein kinase.

Effect of lactation on maternal body weight: a systematic review.

UNLABELLED: The impact of lactation on maternal weight after delivery remains unclear. To address this question, we performed a systematic review of the literature. We searched PubMed, POPLINE, EMBASE, and LILACS computerized databases for relevant articles and classified the evidence using the U.S. Preventive Services Task Force rating system. We found 42 studies, of which 28 contained relevant information: 15 prospective cohort studies, 1 retrospective cohort study, 1 cross-sectional study, and 11 case-series reports. The methods used in these studies varied widely, thus precluding aggregation of results. Level II-2 and III evidence supports a class "C" recommendation: insufficient evidence exists to support an effect of lactation on maternal weight after delivery. Better longitudinal studies with a clear definition of breast-feeding; clear, specific outcome measures; study periods extending 1 or 2 years after delivery; and better control of potentially confounding factors will be needed to resolve this question. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to compile the literature on the effect of lactation on maternal weight, to compare the various studies, and to summarize the data on the effect of lactation on maternal weight gain.