Functional limitations and workdays lost associated with chronic rhinosinusitis and allergic rhinitis

Background: Chronic rhinosinusitis (CRS) and allergic rhinitis are associated with functional limitations, but these impacts are not known on a population basis. Our objective was to epidemiologically determine functional limitations and workdays lost that are associated with CRS and allergic rhinitis in adults. Methods: The Medical Expenditure Panel Survey for calendar year 2007 was examined to identify cases of CRS and allergic rhinitis. Functional limitation variables for activity limitation, work limitation, social limitation, and cognitive limitation determined by the survey also were extracted. Using multivariate models adjusting for age, gender, race, ethnicity, education level, insurance status, geographic region, as well as the Charlson comorbidity index, incremental differences in workdays lost and these functional limitations were determined for patients with and without CRS and allergic rhinitis. Results: Among 225.1 million adults, the prevalences of CRS and allergic rhinitis were 4.9 ± 0.2% and 7.9 ± 0.3%, respectively. Patients with CRS demonstrated an incremental 1.04 ± 0.3 workdays lost per year along with significant increased adjusted odds ratios for activity limitation (odds ratio, 1.54), work limitation (1.50), and social limitation (1.49, all p < .005) but not cognitive limitation (1.05, p = .213). Patients with allergic rhinitis demonstrated an incremental 0.60 ± 0.45 workdays lost along with significant increased adjusted odds ratios for activity limitation (1.42), work limitation (1.43), social limitation (1.47), and cognitive limitation (1.32, all p < .019). Conclusions: Both CRS and allergic rhinitis impart significantly increased odds ratios for activity, work, and social limitations. Allergic rhinitis also carries with it statistically significant odds of functional cognitive limitation. The total aggregate workdays missed in the United States may be estimated at 11.5 million workdays and 10.7 million workdays for CRS and allergic rhinitis, respectively

Burden of disease in chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammation-mediated disease of the nasal mucosa and paranasal sinuses with an under-recognized clinical, humanistic, and economic burden. Patients with CRSwNP experience a high symptom burden, including nasal congestion, loss of smell, and rhinorrhea, which has a negative impact on physical and mental health-related quality of life, including sleep quality. Existing medical and surgical interventions, including local and systemic corticosteroids and endoscopic sinus surgery, may be associated with recurrence of nasal polyps and associated symptoms and with an increased risk of short- and long-term adverse effects, especially with repeated or long-term use. Because type 2 inflammation is implicated in the pathogenesis of several coexisting diseases, patients with CRSwNP often have comorbid asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. These patients, as well as those with high corticosteroid use and/or sinonasal surgical history, have more severe disease and associated symptom burden and represent a difficult-to-treat population under the existing management paradigm. This article reviews the clinical, humanistic, and economic burden of CRSwNP; it highlights the unmet need for effective and safe CRSwNP therapies that effectively control symptoms and minimize recurrence by targeting the underlying type 2 inflammatory disease pathophysiology

A note on the M2-M5 brane system and fuzzy spheres

This note covers various aspects of recent attempts to describe membranes ending on fivebranes using fuzzy geometry. In particular, we examine the Basu-Harvey equation and its relation to the Nahm equation as well as the consequences of using a non-associative algebra for the fuzzy three-sphere. This produces the tantalising result that the fuzzy funnel solution corresponding to Q coincident membranes ending on a five-brane has $Q^{3/2}$ degrees of freedom.Comment: 17 pages, late

Origin of conductivity cross over in entangled multi-walled carbon nanotube network filled by iron

A realistic transport model showing the interplay of the hopping transport between the outer shells of iron filled entangled multi-walled carbon nanotubes (MWNT) and the diffusive transport through the inner part of the tubes, as a function of the filling percentage, is developed. This model is based on low-temperature electrical resistivity and magneto-resistance (MR) measurements. The conductivity at low temperatures showed a crossover from Efros-Shklovski (E-S) variable range hopping (VRH) to Mott VRH in 3 dimensions (3D) between the neighboring tubes as the iron weight percentage is increased from 11% to 19% in the MWNTs. The MR in the hopping regime is strongly dependent on temperature as well as magnetic field and shows both positive and negative signs, which are discussed in terms of wave function shrinkage and quantum interference effects, respectively. A further increase of the iron percentage from 19% to 31% gives a conductivity crossover from Mott VRH to 3D weak localization (WL). This change is ascribed to the formation of long iron nanowires at the core of the nanotubes, which yields a long dephasing length (e.g. 30 nm) at the lowest measured temperature. Although the overall transport in this network is described by a 3D WL model, the weak temperature dependence of inelastic scattering length expressed as L_phi ~T^-0.3 suggests the possibility for the presence of one-dimensional channels in the network due to the formation of long Fe nanowires inside the tubes, which might introduce an alignment in the random structure.Comment: 29 pages,10 figures, 2 tables, submitted to Phys. Rev.

District decision-making for health in low-income settings: a qualitative study in Uttar Pradesh, India, on engaging the private health sector in sharing health-related data.

Health information systems are an important planning and monitoring tool for public health services, but may lack information from the private health sector. In this fourth article in a series on district decision-making for health, we assessed the extent of maternal, newborn and child health (MNCH)-related data sharing between the private and public sectors in two districts of Uttar Pradesh, India; analysed barriers to data sharing; and identified key inputs required for data sharing. Between March 2013 and August 2014, we conducted 74 key informant interviews at national, state and district levels. Respondents were stakeholders from national, state and district health departments, professional associations, non-governmental programmes and private commercial health facilities with 3-200 beds. Qualitative data were analysed using a framework based on a priori and emerging themes. Private facilities registered for ultrasounds and abortions submitted standardized records on these services, which is compulsory under Indian laws. Data sharing for other services was weak, but most facilities maintained basic records related to institutional deliveries and newborns. Public health facilities in blocks collected these data from a few private facilities using different methods. The major barriers to data sharing included the public sector's non-standardized data collection and utilization systems for MNCH and lack of communication and follow up with private facilities. Private facilities feared information disclosure and the additional burden of reporting, but were willing to share data if asked officially, provided the process was simple and they were assured of confidentiality. Unregistered facilities, managed by providers without a biomedical qualification, also conducted institutional deliveries, but were outside any reporting loops. Our findings suggest that even without legislation, the public sector could set up an effective MNCH data sharing strategy with private registered facilities by developing a standardized and simple system with consistent communication and follow up

Exploring electronic effects on the partitioning of actinides(III) from lanthanides(III) using functionalised bis-triazinyl phenanthroline ligands

The first examples of 4,7-disubstituted 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzo-triazin-3-yl)-1,10- phenanthroline (CyMe4 -BTPhen) ligands are reported herein. Evaluating the kinetics, selectivity and stoichiometry of actinide(III) and lanthanide(III) radiotracer extractions has provided a mechanistic insight into the extraction process. For the first time, it has been demonstrated that metal ion extraction kinetics can be modulated by backbone functionalisation and a promising new CHON compliant candidate ligand with enhanced metal ion extraction kinetics has been identified. The effects of 4,7- functionalisation on the equilibrium metal ion distribution ratios are far more pronounced than those of 5,6-functionalisation. The complexation of Cm(III) with two of the functionalised ligands was investigated by TRLFS and, at equilibrium, species of 1:2 [M:L] stoichiometry were observed exclusively. A direct correlation between the ELUMO-EHOMO energy gap and metal ion extraction potential is reported, with DFT studies reaffirming experimental findings

CCN2 Is Required for the TGF-β Induced Activation of Smad1 - Erk1/2 Signaling Network

Connective tissue growth factor (CCN2) is a multifunctional matricellular protein, which is frequently overexpressed during organ fibrosis. CCN2 is a mediator of the pro-fibrotic effects of TGF-β in cultured cells, but the specific function of CCN2 in the fibrotic process has not been elucidated. In this study we characterized the CCN2-dependent signaling pathways that are required for the TGF-β induced fibrogenic response. By depleting endogenous CCN2 we show that CCN2 is indispensable for the TGF-β-induced phosphorylation of Smad1 and Erk1/2, but it is unnecessary for the activation of Smad3. TGF-β stimulation triggered formation of the CCN2/β3 integrin protein complexes and activation of Src signaling. Furthermore, we demonstrated that signaling through the αvβ3 integrin receptor and Src was required for the TGF-β induced Smad1 phosphorylation. Recombinant CCN2 activated Src and Erk1/2 signaling, and induced phosphorylation of Fli1, but was unable to stimulate Smad1 or Smad3 phosphorylation. Additional experiments were performed to investigate the role of CCN2 in collagen production. Consistent with the previous studies, blockade of CCN2 abrogated TGF-β-induced collagen mRNA and protein levels. Recombinant CCN2 potently stimulated collagen mRNA levels and upregulated activity of the COL1A2 promoter, however CCN2 was a weak inducer of collagen protein levels. CCN2 stimulation of collagen was dose-dependent with the lower doses (<50 ng/ml) having a stimulatory effect and higher doses having an inhibitory effect on collagen gene expression. In conclusion, our study defines a novel CCN2/αvβ3 integrin/Src/Smad1 axis that contributes to the pro-fibrotic TGF-β signaling and suggests that blockade of this pathway may be beneficial for the treatment of fibrosis

Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs)

Cardiac fibroblasts (CF) are well-established as key regulators of extracellular matrix (ECM) turnover in the context of myocardial remodelling and fibrosis. Recently, this cell type has also been shown to act as a sensor of myocardial damage by detecting and responding to damage-associated molecular patterns (DAMPs) upregulated with cardiac injury. CF express a range of innate immunity pattern recognition receptors (TLRs, NLRs, IL-1R1, RAGE) that are stimulated by a host of different DAMPs that are evident in the injured or remodelling myocardium. These include intracellular molecules released by necrotic cells (heat shock proteins, high mobility group box 1 protein, S100 proteins), proinflammatory cytokines (interleukin-1α), specific ECM molecules up-regulated in response to tissue injury (fibronectin-EDA, tenascin-C) or molecules modified by a pathological environment (advanced glycation end product-modified proteins observed with diabetes). DAMP receptor activation on fibroblasts is coupled to altered cellular function including changes in proliferation, migration, myofibroblast transdifferentiation, ECM turnover and production of fibrotic and inflammatory paracrine factors, which directly impact on the heart's ability to respond to injury. This review gives an overview of the important role played by CF in responding to myocardial DAMPs and how the DAMP/CF axis could be exploited experimentally and therapeutically