Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis (CF) is caused by mutations in the <it>CFTR </it>gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl^-channel, would improve the intestinal phenotype in CF mice.</p> <p>Methods</p> <p><it>Cftr^tm1UNC</it>(CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16<it>S </it>gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR.</p> <p>Results</p> <p>Crypt width in control CF mice was 700% that of WT mice (<it>P </it>< 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (<it>P </it>= 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (<it>P </it>= 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (<it>P </it>= 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (<it>P </it>< 0.001) and CF mice (<it>P </it>< 0.001). Lubiprostone enhanced small intestinal transit in WT mice (<it>P </it>= 0.024) but not in CF mice (<it>P </it>= 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels.</p> <p>Conclusions</p> <p>These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.</p

Winding number order in the Haldane model with interactions

We study the Haldane model with nearest–neighbor interactions. This model is physically motivated by the associated implementation with ultracold atoms. We show that the topological phase of the interacting model can be characterized by a physically observable winding number. The robustness of this number extends well beyond the topological insulator phase towards attractive and repulsive interactions that are comparable to the kinetic energy scale of the model. We identify and characterize the relevant phases of the model as a function of the interaction strength

Nested defects on the boundary of topological superconductors

Helical Majorana edge states at the 2D boundaries of 3D topological superconductors can be gapped by a surface Zeeman field. Here we study the effect nested defects imprinted on the Zeeman field can have on the edge states. We demonstrate that depending on the configuration of the field, we can induce dimensional reduction of gapless Majorana modes from 2D to 1D or quasi-0D at magnetic domain walls. We determine the nature of the Majorana localization on these defects as a function of the magnitude and configuration of the Zeeman field. Finally, we observe a generalization of the index theorem governing the number of gapless modes at the interface between topologically nontrivial systems with partial Chern numbers

Induced Topological Phases at the Boundary of 3D Topological Superconductors

We present tight-binding models of 3D topological superconductors in class DIII that support a variety of winding numbers. We show that gapless Majorana surface states emerge at their boundary in agreement with the bulk-boundary correspondence. At the presence of a Zeeman field, the surface states become gapped and the boundary behaves as a 2D superconductor in class D. Importantly, the 2D and 3D winding numbers are in agreement, signifying that the topological phase of the boundary is induced by the phase of the 3D bulk. Hence, the boundary of a 3D topological superconductor in class DIII can be used for the robust realization of localized Majorana zero modes

Detection of Chern numbers and entanglement in topological two-species systems through subsystem winding numbers

Topological invariants, such as the Chern number, characterize topological phases of matter. Here we provide a method to detect Chern numbers in systems with two distinct species of fermion, such as spins, orbitals or several atomic states. We analytically show that the Chern number can be decomposed as a sum of component specific winding numbers, which are themselves physically observable. We apply this method to two systems, the quantum spin Hall insulator and a staggered topological superconductor, and show that (spin) Chern numbers are accurately reproduced. The measurements required for constructing the component winding numbers also enable one to probe the entanglement spectrum with respect to component partitions. Our method is particularly suited to experiments with cold atoms in optical lattices where time-of-flight images can give direct access to the relevant observables

Diseño y construcción de las bóvedas por cruceros en España durante el siglo XVI

The aim of this text is to present the historical guidelines, design and construction of the grid crossing vaults built in Spain during the 16th century to show how the Gothic tradition of building ribbed vaults could be adapted to classical aesthetic principles. In the Andalusia of the 16th century, both a Renaissance classical architecture and another extraordinarily evolved Gothic one reached, at the same time, their full development, taking place between them interesting knowledge, stylistic and technical transfers. In this respect, the grid crossing vaults are a remarkable example of the formal autonomy of Gothic ribs which, without losing their medieval construction principles, are capable of adapting themselves to Renaissance models. We will see how in the grid crossing vaults, the Gothic crossings adapted themselves to the shape of a classical grid structure, drawing on the surface of the vault a design of caissons according to the stricter Roman Canon.El objetivo de este texto es dar a conocer las pautas históricas, de diseño y construcción de las bóvedas por cruceros erigidas en España durante el siglo XVI, como muestra de cómo la tradición gótica de construir bóvedas con nervaduras pudo adaptarse a los principios estéticos clásicos. En la Andalucía del siglo XVI, una arquitectura clásica renacentista y otra gótica extraordinariamente evolucionada alcanzaron, al mismo tiempo, su pleno desarrollo; entre ambas se produjeron interesantes transferencias de conocimiento, estilísticas y técnicas. En este sentido, las bóvedas por cruceros constituyen un notable ejemplo de autonomía formal de la nervadura gótica que, sin perder sus principios constructivos medievales, es capaz de adaptarse a modelos renacentistas. Veremos como en las bóvedas por cruceros, las crucerías góticas se adaptan a la forma de una trama reticular clásica, dibujando sobre la superficie de la bóveda un diseño de casetones conforme al canon romano más estricto

Student evaluation of an OSCE in paediatrics at the University of the West Indies, Jamaica

BACKGROUND: The Faculty of Medical Sciences, University of the West Indies first implemented the Objective Structured Clinical Examination (OSCE) in the final MB Examination in Medicine and Therapeutics during the 2000–2001 academic year. Simultaneously, the Child Health Department initiated faculty and student training, and instituted the OSCE as an assessment instrument during the Child Health (Paediatric) clerkship in year 5. The study set out to explore student acceptance of the OSCE as part of an evaluation of the Child Health clerkship. METHODS: A self-administered questionnaire was completed by successive groups of students immediately after the OSCE at the end of each clerkship rotation. Main outcome measures were student perception of examination attributes, which included the quality of instructions and organisation, the quality of performance, authenticity and transparency of the process, and usefulness of the OSCE as an assessment instrument compared to other formats. RESULTS: There was overwhelming acceptance of the OSCE in Child Health with respect to the comprehensiveness (90%), transparency (87%), fairness (70%) and authenticity of the required tasks (58–78%). However, students felt that it was a strong anxiety-producing experience. And concerns were expressed regarding the ambiguity of some questions and inadequacy of time for expected tasks. CONCLUSION: Student feedback was invaluable in influencing faculty teaching, curriculum direction and appreciation of student opinion. Further psychometric evaluation will strengthen the development of the OSCE

Work-Related Mental Health and Job Performance: Can Mindfulness Help?

Work-related mental health issues such as work-related stress and addiction to work impose a significant health and economic burden to the employee, the employing organization, and the country of work more generally. Interventions that can be empirically shown to improve levels of work-related mental health – especially those with the potential to concurrently improve employee levels of work performance – are of particular interest to occupational stakeholders. One such broad-application interventional approach currently of interest to occupational stakeholders in this respect is mindfulness-based interventions (MBIs). Following a brief explication of the mindfulness construct, this paper critically discusses current research directions in the utilization of mindfulness in workplace settings and assesses its suitability for operationalization as an organization-level work-related mental health intervention. By effecting a perceptual-shift in the mode of responding and relating to sensory and cognitive-affective stimuli, employees that undergo mindfulness training may be able to transfer the locus of control for stress from external work conditions to internal metacognitive and attentional resources. Therefore, MBIs may constitute cost-effective organization-level interventions due to not actually requiring any modifications to human resource management systems and practises. Based on preliminary empirical findings and on the outcomes of MBI studies with clinical populations, it is concluded that MBIs appear to be viable interventional options for organizations wishing to improve the mental health of their employees

Fungicide resistance management in Australian grain crops

Fungicide resistance is a serious and increasing problem in cropping systems worldwide. Fungicides are an important component of integrated disease management strategies for the protection of crops from the impacts of fungal diseases. However, as their use has increased, the effectiveness of some fungicides has been reduced by the development of fungicide resistant pathogen populations. Without intervention, more fungicides are likely to become ineffective

Sentinel-based Surveillance of Coyotes to Detect Bovine Tuberculosis, Michigan

Coyotes could be used as sentinels to detect Mycobacterium bovis in the wild