Topical Corticosteroids Normalize both Skin and Systemic Inflammatory Markers in Infant Atopic Dermatitis

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease. It is highly heterogeneous in clinical presentation, treatment response, disease trajectory and associated atopic comorbidities. Immune biomarkers are dysregulated in skin and peripheral blood. Aims: We used noninvasive skin and peripheral biomarkers to observe the effects of real-world topical corticosteroid (TCS) treatment in infants with AD, by measuring skin and blood biomarkers before and after therapy. Methods: Seventy-four treatment-naïve infants with AD underwent 6 weeks of TCS treatment. Stratum corneum (SC) and plasma blood biomarkers as well as SC natural moisturizing factor (NMF) were measured before and after TCS therapy. Immune markers included innate, T helper (Th)1 and Th2 immunity, angiogenesis, and vascular factors. AD severity was assessed by the Scoring Atopic Dermatitis index, and skin barrier function by transepidermal water loss (TEWL). Twenty healthy infants were recruited as controls. Results: TCS therapy predictably led to improvement in disease severity. Levels of immune markers in the skin and in the peripheral blood showed significant change from baseline, though most did not reach healthy control levels. The most prominent change from baseline in the SC was in markers of innate immune activation, interleukin (IL)-18, IL-8 and IL-1α, and the Th2 chemokines C-C motif chemokine (CCL)17 and CCL22. In blood, the largest changes were in Th2-skewed biomarkers: CCL17, IL-13, CCL22, IL-5, and CCL26. TEWL decreased after therapy; no significant changes from baseline were found for NMF. Conclusions: The profound impact of topical therapy on systemic biomarkers suggests that the skin compartment generates a major component of dysregulated systemic cytokines in infant AD. There may be long-term beneficial effects of correcting systemic immune dysregulation through topical therapy

Stationary axisymmetric exteriors for perturbations of isolated bodies in general relativity, to second order

Perturbed stationary axisymmetric isolated bodies, e.g. stars, represented by a matter-filled interior and an asymptotically flat vacuum exterior joined at a surface where the Darmois matching conditions are satisfied, are considered. The initial state is assumed to be static. The perturbations of the matching conditions are derived and used as boundary conditions for the perturbed Ernst equations in the exterior region. The perturbations are calculated to second order. The boundary conditions are overdetermined: necessary and sufficient conditions for their compatibility are derived. The special case of perturbations of spherical bodies is given in detail.Comment: RevTeX; 32 pp. Accepted by Phys. Rev. D. Added references and extra comments in introductio

The molecular genetic analysis of the expanding pachyonychia congenita case collection

BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma and nail dystrophy, often accompanied by oral leucokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16 or KRT17. OBJECTIVES: To identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry during the last few years. METHODS: Genomic DNA isolated from saliva or peripheral blood leucocytes was amplified using primers specific for the PC-associated keratin genes and polymerase chain reaction products were directly sequenced. RESULTS: Mutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105. CONCLUSIONS: By identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17, this study has confirmed, at the molecular level, the clinical diagnosis of PC in these families

Heterozygous frameshift mutation in keratin 5 in a family with Galli-Galli disease

BACKGROUND: Reticulate pigmentary disorders include the rare autosomal dominant Galli–Galli disease (GGD) and Dowling–Degos disease (DDD). Clinical diagnosis between some of the subtypes can be difficult due to a degree of overlap between clinical features, therefore analysis at the molecular level may be necessary to confirm the diagnosis. OBJECTIVES: To identify the underlying genetic defect in a 48-year-old Asian-American woman with a clinical diagnosis of GGD. METHODS: Histological analysis was performed on a skin biopsy using haematoxylin–eosin staining. KRT5 (the gene encoding keratin 5) was amplified from genomic DNA and directly sequenced. RESULTS: The patient had a history of pruritus and hyperpigmented erythematous macules and thin papules along the flexor surfaces of her arms, her upper back and neck, axillae and inframammary areas. Hypopigmented macules were seen among the hyperpigmentation. A heterozygous 1-bp insertion mutation in KRT5 (c.38dupG; p.Ser14GlnfsTer3) was identified in the proband. This mutation occurs within the head domain of the keratin 5 protein leading to a frameshift and premature stop codon. CONCLUSIONS: From the histological findings and mutation analysis the individual was identified as having GGD due to haploinsufficiency of keratin 5

A thermionic energy converter with a molybdenum-alumina cermet emitter

A study is made of the properties of cermets as electrode materials for thermionic energy converters. For thermodynamic reasons it is expected that all cermets composed of pure Mo and refractory oxides have the same bare work function. From data on the work function of Mo in an oxygen atmosphere this bare work function is estimated to be F=4.9 eV (at T=1400¿°C). Experimentally, the bare work function of Al2O3-Mo cermets was found to be F=4.5 eV, independent of the relative amounts of Al2O3 and Mo. The cesiated work function of the Al2O3-Mo cermets was found to be 0.15 eV lower than the cesiated work function of pure Mo. The bare work function of Mo3Al was found to be F=4.0 eV. The cesiated work function of Mo3Al at collector temperature conditions was 0.3 eV lower than the cesiated work function of pure Mo. The electrical power density of a diode with an Al2O3-Mo cermet emitter was 0.4 W/cm2 at 1300¿°C. The barrier index at this temperature was 2.36 V. The high barrier index is attributed to a high plasma voltage drop Vd=0.91 V

Dynamics of Metal Centers Monitored by Nuclear Inelastic Scattering

Nuclear inelastic scattering of synchrotron radiation has been used now since 10 years as a tool for vibrational spectroscopy. This method has turned out especially useful in case of large molecules that contain a M\"ossbauer active metal center. Recent applications to iron-sulfur proteins, to iron(II) spin crossover complexes and to tin-DNA complexes are discussed. Special emphasis is given to the combination of nuclear inelastic scattering and density functional calculations

In vivo dual RNA-seq reveals that neutrophil recruitment underlies differential tissue tropism of Streptococcus pneumoniae.

Streptococcus pneumoniae is a genetically diverse human-adapted pathogen commonly carried asymptomatically in the nasopharynx. We have recently shown that a single nucleotide polymorphism (SNP) in the raffinose pathway regulatory gene rafR accounts for a difference in the capacity of clonally-related strains to cause localised versus systemic infection. Using dual RNA-seq, we show that this SNP affects expression of bacterial genes encoding multiple sugar transporters, and fine-tunes carbohydrate metabolism, along with extensive rewiring of host transcriptional responses to infection, particularly expression of genes encoding cytokine and chemokine ligands and receptors. The data predict a crucial role for differential neutrophil recruitment (confirmed by in vivo neutrophil depletion and IL-17 neutralization) indicating that early detection of bacteria by the host in the lung environment is crucial for effective clearance. Thus, dual RNA-seq provides a powerful tool for understanding complex host-pathogen interactions and reveals how a single bacterial SNP can drive differential disease outcomes