Effects of cigarette smoking on the respiratory epithelium and its role in the pathogenesis of chronic rhinosinusitis

O crescente consumo de cigarro tem despertado preocupações com o desenvolvimento e agravamento de doenças, em especial às relacionadas ao trato respiratório. OBJETIVO: Neste artigo revisamos as evidências que apontam os efeitos da fumaça de cigarro sobre o epitélio respiratório bem como o seu papel na fisiopatogenia na rinossinusite crônica. CONCLUSÃO: Embora existam dados que fortaleçam um vínculo entre o hábito de fumar e a RSC, em seu conjunto, os estudos demonstram que deve haver grande dependência da susceptibilidade individual na resposta à fumaça de cigarro para o desenvolvimento ou manutenção da RSC. Uma adequada orientação a esses pacientes para interrupção do consumo de cigarro, assim como o reforço de campanhas de combate ao tabagismo, são de extrema importância para o controle dessa doença de grande impacto sócio-econômico.The increasing consumption of cigarettes has aroused concerns about the development and worsening of diseases, particularly those related to the respiratory tract. AIM: In this paper we review the evidence suggesting the effects of cigarette smoking on the respiratory epithelium and its role in the pathogenesis in chronic rhinosinusitis. CONCLUSIONS: Although there is evidence supporting a link between smoking and CRS, studies suggest that there might be individual susceptibility to cigarette smoking causing the development and/or maintenance of CRS. Proper patient educations to quit smoking as well as reinforcement of antismoking campaigns are extremely important to control this disease of major socio-economic impact

Secondhand smoke inhibits both Cl- and K+ conductances in normal human bronchial epithelial cells

Secondhand smoke (SHS) exposure is an independent risk factor for asthma, rhinosinusitis, and more severe respiratory tract infections in children and adults. Impaired mucociliary clearance with subsequent mucus retention contributes to the pathophysiology of each of these diseases, suggesting that altered epithelial salt and water transport may play an etiological role. To test the hypothesis that SHS would alter epithelial ion transport, we designed a system for in vitro exposure of mature, well-differentiated human bronchial epithelial cells to SHS. We show that SHS exposure inhibits cAMP-stimulated, bumetanide-sensitive anion secretion by 25 to 40% in a time-dependent fashion in these cells. Increasing the amount of carbon monoxide to 100 ppm from 5 ppm did not increase the amount of inhibition, and filtering SHS reduced inhibition significantly. It was determined that SHS inhibited cAMP-dependent apical membrane chloride conductance by 25% and Ba2+-sensitive basolateral membrane potassium conductance by 50%. These data confirm previous findings that cigarette smoke inhibits chloride secretion in a novel model of smoke exposure designed to mimic SHS exposure. They also extend previous findings to demonstrate an effect on basolateral K+ conductance. Therefore, pharmacological agents that increase either apical membrane chloride conductance or basolateral membrane potassium conductance might be of therapeutic benefit in patients with diseases related to SHS exposure

Universal dynamical decoherence control of noisy single-and multi-qubit systems

In this article we develop, step by step, the framework for universal dynamical control of two-level systems (TLS) or qubits experiencing amplitude- or phase-noise (AN or PN) due to coupling to a thermal bath. A comprehensive arsenal of modulation schemes is introduced and applied to either AN or PN, resulting in completely analogous formulae for the decoherence rates, thus underscoring the unified nature of this universal formalism. We then address the extension of this formalism to multipartite decoherence control, where symmetries are exploited to overcome decoherence.Comment: 28 pages, 4 figure

Macrophages promote epithelial proliferation following infectious and non-infectious lung injury through a Trefoil factor 2-dependent mechanism.

Coordinated efforts between macrophages and epithelia are considered essential for wound healing, but the macrophage-derived molecules responsible for repair are poorly defined. This work demonstrates that lung macrophages rely upon Trefoil factor 2 to promote epithelial proliferation following damage caused by sterile wounding, Nippostrongylus brasiliensis or Bleomycin sulfate. Unexpectedly, the presence of T, B, or ILC populations was not essential for macrophage-driven repair. Instead, conditional deletion of TFF2 in myeloid-restricted CD11cCre TFF2 flox mice exacerbated lung pathology and reduced the proliferative expansion of CD45- EpCAM+ pro-SPC+ alveolar type 2 cells. TFF2 deficient macrophages had reduced expression of the Wnt genes Wnt4 and Wnt16 and reconstitution of hookworm-infected CD11cCre TFF2flox mice with rWnt4 and rWnt16 restored the proliferative defect in lung epithelia post-injury. These data reveal a previously unrecognized mechanism wherein lung myeloid phagocytes utilize a TFF2/Wnt axis as a mechanism that drives epithelial proliferation following lung injury

Physical Results from Unphysical Simulations

We calculate various properties of pseudoscalar mesons in partially quenched QCD using chiral perturbation theory through next-to-leading order. Our results can be used to extrapolate to QCD from partially quenched simulations, as long as the latter use three light dynamical quarks. In other words, one can use unphysical simulations to extract physical quantities - in this case the quark masses, meson decay constants, and the Gasser-Leutwyler parameters L_4-L_8. Our proposal for determining L_7 makes explicit use of an unphysical (yet measurable) effect of partially quenched theories, namely the double-pole that appears in certain two-point correlation functions. Most of our calculations are done for sea quarks having up to three different masses, except for our result for L_7, which is derived for degenerate sea quarks.Comment: 26 pages, 12 figures (discussion on discretization errors at end of sec. IV clarified; minor improvements in presentation; results unchanged

CALHM1-Mediated ATP Release and Ciliary Beat Frequency Modulation in Nasal Epithelial Cells

Mechanical stimulation of airway epithelial cells causes apical release of ATP, which increases ciliary beat frequency (CBF) and speeds up mucociliary clearance. The mechanisms responsible for this ATP release are poorly understood. CALHM1, a transmembrane protein with shared structural features to connexins and pannexins, has been implicated in ATP release from taste buds, but it has not been evaluated for a functional role in the airway. In the present study, Calhm1 knockout, Panx1 knockout, and wild-type mouse nasal septal epithelial cells were grown at an air-liquid interface (ALI) and subjected to light mechanical stimulation from an air puff. Apical ATP release was attenuated in Calhm1 knockout cultures following mechanical stimulation at a pressure of 55 mmHg for 50 milliseconds (p \u3c 0.05). Addition of carbenoxolone, a PANX1 channel blocker, completely abolished ATP release in Calhm1 knockout cultures but not in wild type or Panx1 knockout cultures. An increase in CBF was observed in wild-type ALIs following mechanical stimulation, and this increase was significantly lower (p \u3c 0.01) in Calhm1 knockout cultures. These results demonstrate that CALHM1 plays a newly defined role, complementary to PANX1, in ATP release and downstream CBF modulation following a mechanical stimulus in airway epithelial cells. © 2017 The Author(s)

Partially quenched chiral perturbation theory without Φ0\Phi_0

This paper completes the argument that lattice simulations of partially quenched QCD can provide quantitative information about QCD itself, with the aid of partially quenched chiral perturbation theory. A barrier to doing this has been the inclusion of $\Phi_0$, the partially quenched generalization of the $\eta'$, in previous calculations in the partially quenched effective theory. This invalidates the low energy perturbative expansion, gives rise to many new unknown parameters, and makes it impossible to reliably calculate the relation between the partially quenched theory and low energy QCD. We show that it is straightforward and natural to formulate partially quenched chiral perturbation theory without $\Phi_0$, and that the resulting theory contains the effective theory for QCD without the $\eta'$. We also show that previous results, obtained including $\Phi_0$, can be reinterpreted as applying to the theory without $\Phi_0$. We contrast the situation with that in the quenched effective theory, where we explain why it is necessary to include $\Phi_0$. We also compare the derivation of chiral perturbation theory in partially quenched QCD with the standard derivation in unquenched QCD. We find that the former cannot be justified as rigorously as the latter, because of the absence of a physical Hilbert space. Finally, we present an encouraging result: unphysical double poles in certain correlation functions in partially quenched chiral perturbation theory can be shown to be a property of the underlying theory, given only the symmetries and some plausible assumptions.Comment: 45 pages, no figure

Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono- and coculture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS

Media, Capabilities, and Justification

In this paper, I evaluate the ‘capability approach’ developed by Amartya Sen and Martha Nussbaum as a normative perspective for critical media research. The concept of capabilities provides a valuable way of assessing media and captures important aspects of the relationship between media and equality. However, following Rainer Forst’s critique of outcome- oriented approaches to justice, I argue the capability approach needs to pay more attention to questions of power and process. In particular, when it comes to deciding which capabilities media should promote and what media structure and practices should promote them, the capability approach must accept the priority of deliberative and democratic processes of justification. Once we do this, we are urged to situate the concept of capabilities within a more process-oriented view of justice, focused not on capabilities as such, but on outlining the conditions required for justificatory equality. After discussing the capability approach, I will outline the process-oriented theory of justice Forst has developed around the idea of the ‘right to justification’. While Forst does not discuss media in depth, I argue his theory of justice can provide a valuable alternative normative standpoint for the critical media research