bluuebunny/crossref_metadata_2025 huggingface dataset:
The paradigmatic pitfalls of customer-centric marketing
Authors: Osborne Phil , Ballantyne David
Published: April 2012

This article will argue that, despite customer-centric intent, marketing theory remains trapped in a firm-centric paradigm. How this apparent contradiction has endured is discussed critically with reference to what we see as four influential marketing perspectives. These perspectives are the 4Ps marketing mix, market-based assets, relationship marketing, and customer equity. Apart from the 4Ps mix, these marketing perspectives are seldom recognized as problematic. We argue that the firm-centric approach to value creation embedded in these four influential frameworks overwhelms marketing’s customer-centric intent. We also address the question, ‘can (or indeed should) marketing management be customer-centric?’ Our conclusion is that new directions of inquiry are needed, and we offer suggestions that might allow marketing the means to break free from its enduring, firm-centric paradigmatic trap
A randomized recruitment intervention trial in Parkinson’s disease to increase participant diversity: early stopping for lack of efficacy
Authors: Tilley Barbara C , Mainous Arch G , Elm Jordan J , Pickelsimer Elisabeth , Soderstrom Lea H , Ford Marvella E , Diaz Vanessa A , Siminoff Laura A , Burau Keith , Smith Daniel W
Published: April 2012

Background Failure to include participants of diverse race and ethnicity (i.e. those other than European Caucasian, non-Hispanic) in clinical trials impedes the safe development of new therapies given the potential for racial/ethnicity-related variations in treatment response. Increasing diversity is problematic for low prevalence diseases, where most community-based approaches do not reach those with the disease.

Purpose Increase racial/ethnic diversity of participants in a Parkinson’s disease therapeutic trial.

Methods We incorporated a randomized Ancillary Trial into the multisite National Institute of Neurologic Disorders and Stroke Exploratory Trials in Parkinson’s Disease Long-Term Study 1. Movement disorders clinics already participating in long-term trial 1 were eligible and were the unit of randomization and analysis. At least 14% of adult residents over age 55 and living within 30 miles of the eligible site were from a diverse population, or there was a near-by zip code with a highly diverse population. Eligible sites also agreed to be randomized. The intervention was designed to increase community physicians’ trust in long-term trial 1 investigators and address recruitment barriers in diverse populations. Primary outcomes included percentage of participants from diverse racial/ethnic groups enrolled in long-term trial 1, and qualitative findings from key informant interviews of the Ancillary Trial investigators and coordinators at the end of the trial.

Results The Ancillary Trial stopped early for lack of efficacy, conditional power less than 1%. The 17 intervention sites had 12.6% diverse participants compared to 15.6% in 15 control clinics; odds ratio 0.82 (95% confidence interval = 0.32−2.16). In key informant interviews, high enrollers of diverse participants reported more use of existing physician relationships, untargeted community outreach, and extensive efforts to overcome participants’ barriers. Low enrollers reported more use of patients in their practices and placed more responsibility for low enrollment on prospective participants.

Limitations The Ancillary Trial included only those with Parkinson’s disease. Whether our findings generalize to trials in other low prevalence diseases is unknown.

Conclusions Increasing diversity in Parkinson’s disease clinical trials requires new paradigms for trial investigator and coordinator interactions with community physicians and prospective trial participants.
Radical sovereignty and control society: Images of late modern sovereignty in Rebeyrolle’s Le Cyclope
Authors: Lippens Ronnie
Published: April 2012

In this contribution it is argued that the late Paul Rebeyrolle’s (1926–2005) painting Le Cyclope (1987) subtly weaves together two images of sovereignty (conceived here as ‘control over emergence’), producing a third which expresses a vision of sovereignty as grounded in creative capacity. In Rebeyrolle’s Le Cyclope, control over emergence is achieved in and through creation. As such this French painter’s work attempts to show a way out of the predominant late modern desire for and will to sovereignty which is all about the radical, relentless and unrelenting flight from law and code. Such a radical and absolute imaginary, it is argued here, is bound to strand itself in paradox, and, ultimately, in the loss of all ‘control over emergence’. The paper also explores the relevance of Rebeyrolle’s images of late modern sovereignty for ‘control society’, in particular for phenomena such as ‘edgework’ and ‘precautionary cultures’.
Leading questions: Leadership, ethics, and administrative evil
Authors: Reed George E
Published: April 2012

Administrative evil is a relatively new ethical concept that originated in the field of Public Administration with the publication of Guy Adams and Danny Balfour’s 1998 book Unmasking Administrative Evil. It describes the phenomenon whereby otherwise well-intentioned individuals participate in systems that cause harm to innocent people. This essay explores the concept and suggests that the implications for leadership studies and practice are worthy of additional exploration. A critique of the concept is provided along with questions that could point the way to additional research.
Minding their business: Discourses of colonialism and neoliberalism in the commercial guide for US companies in China
Authors: Ban Zhuo , Dutta Mohan Jyoti
Published: April 2012

In recent years, China has emerged as a major economic and trade partner of the USA. In the light of the increasing ‘neoliberalization’ of the Chinese economy – as exemplified by privatization, deregulation and globalization, China has come to be situated in the economic and political imagination within mainstream managerial US discourses of commerce and trade. As a strategic economic partner for US-based businesses, much academic, policy-based, and commercial literature has focused on ‘relationship management’ issues to guide US-based business management practices directed toward China. In this article, we focus on the discourses of ‘relationship management’ in the 2009 through 2011 versions of one such document: Doing Business in China: Country Commercial Guide for US Companies, a publication of the US and Foreign Commercial Service and the US Department of State. Using an entry point for putting the postcolonial and ‘political economy’ theoretical frameworks in conversation, as exemplified by the works of Edward Said, Arif Dirlik, and David Harvey, this document was analyzed for congruent themes and the ways in which these themes depicted the relationships of power and control within contemporary configurations of neocolonialism. Three themes were reflected in the discourse: (1) China as a juvenile business field; (2) primitive business culture of the Orient; and (3) globalization as improvement and development. These themes were examined in detail and explicated in relation to postcolonial and neoliberal political economic theories, elucidating the relationship among neoliberalization, the nation state and neocolonial framing of the Orient.
African American Students’ Participation in Online Distance Education in STEM Disciplines
Authors: Flowers Lawrence O. , White Erin N. , Raynor James E. , Bhattacharya Sambit
Published: April 2012

Despite the increase in online distant learning initiatives at many of the nation’s colleges and universities, collectively, Historically Black Colleges and Universities (HBCUs) continue to lag behind non-HBCUs in the development and implementation of online courses and programs. Data produced by the National Center for Education Statistics show that African American students are enrolled in significantly less distance education courses when compared with White students. In addition, there is a substantial disparity in the number of online science, technology, engineering, and mathematics (STEM) courses and programs when compared with online courses and programs in education, business, or the social sciences at HBCUs. The primary aim of this article is to examine data that explore African American students’ participation in distance education in STEM disciplines. Recommendations for future research are also discussed in this article.
Human cytomegalovirus-encoded UL33 and UL78 heteromerize with host CCR5 and CXCR4 impairing their HIV coreceptor activity
Authors: Tadagaki Kenjiro , Tudor Daniela , Gbahou Florence , Tschische Pia , Waldhoer Maria , Bomsel Morgane , Jockers Ralf , Kamal Maud
Published: April 2012

Human cytomegalovirus (HCMV) encodes four 7-transmembrane-spanning (7TM) proteins, US28, US27, UL33, and UL78, which present important sequence homology with human chemokine receptors. Whereas US28 binds a large range of chemokines and disturbs host cell signaling at different levels, the others are orphans with largely unknown functions. Assembly of 2 different 7TM proteins into hetero-oligomeric complexes may profoundly change their respective functional properties. We show that HCMV-encoded UL33 and UL78 form heteromers with CCR5 and CXCR4 chemokine receptors in transfected human embryonic kidney 293T cells and monocytic THP-1 cells. Expression of UL33 and UL78 had pleiotropic, predominantly negative, effects on CCR5 and CXCR4 cell surface expression, ligand-induced internalization, signal transduction, and migration without modifying the chemokine binding properties of CCR5 and CXCR4. Importantly, the coreceptor activity of CCR5 and CXCR4 for HIV was largely impaired in the presence of UL33 and UL78 without affecting expression of the primary HIV entry receptor CD4 and its interaction with CCR5 and CXCR4. Collectively, we identified the first molecular function for the HCMV-encoded orphan UL33 and UL78 7TM proteins, namely the regulation of cellular chemokine receptors through receptor heteromerization.
HHV-8–encoded viral IL-6 collaborates with mouse IL-6 in the development of multicentric Castleman disease in mice
Authors: Suthaus Jan , Stuhlmann-Laeisz Christiane , Tompkins Van S. , Rosean Timothy R. , Klapper Wolfram , Tosato Giovanna , Janz Siegfried , Scheller Jürgen , Rose-John Stefan
Published: April 2012

Human herpes virus 8 (HHV-8) or Kaposi sarcoma-associated herpes virus is the etiologic agent of Kaposi sarcoma, primary effusion lymphoma, and plasma cell-type multicentric Castleman disease (MCD). HHV-8 encodes a viral homolog of human IL-6, called viral IL-6 (vIL-6), which does not require the cellular IL-6 receptor for binding to the ubiquitously expressed gp130 receptor subunit and subsequent JAK-STAT signaling. Thus, in contrast to IL-6, vIL-6 can stimulate virtually all cells in the body. To elucidate the mechanism by which vIL-6 drives human diseases, we generated transgenic mice that constitutively express vIL-6 under control of the MHC class I promoter. The mice were found to exhibit vIL-6 serum levels comparable with those observed in HHV-8–infected patients, to contain elevated amounts of phosphorylated STAT3 in spleen and lymph nodes, where vIL-6 was produced, and to spontaneously develop key features of human plasma cell-type MCD, including splenomegaly, multifocal lymphadenopathy, hypergammaglobulin-emia, and plasmacytosis. Transfer of the vIL-6 transgene onto an IL-6–deficient genetic background abrogated MCD-like phenotypes, indicating that endogenous mouse IL-6 is a crucial cofactor in the natural history of the disease. Our results in mice suggest that human IL-6 plays an important role in the pathogenesis of HHV-8–associated MCD.
Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes
Authors: Brunstein Claudio G. , Eapen Mary , Ahn Kwang Woo , Appelbaum Frederick R. , Ballen Karen K. , Champlin Richard E. , Cutler Corey , Kan Fangyu , Laughlin Mary J. , Soiffer Robert J. , Weisdorf Daniel J. , Woolfrey Anne , Wagner John E.
Published: April 2012

We report the relative efficacy of co-infusing 2 umbilical cord blood units (dUCB) compared with peripheral blood progenitor cells (PBPCs) from 8 of 8 or 7 of 8 HLA-matched unrelated donors. All patients received reduced-intensity conditioning (RIC) regimens. Four treatment groups were evaluated: 4-6 of 6 matched dUCB-TCF (n = 120; TCF = total body irradiation [TBI] 200 cGy + cyclophos-phamide + fludarabine), 4-6 of 6 matched dUCB-other (n = 40; alkylating agent + fludarabine ± TBI), and 8 of 8 (n = 313) and 7 of 8 HLA-matched PBPCs (n = 111). Compared with matched 8 of 8 PBPC transplantations, transplantation-related mortality (TRM), and overall mortality were similar after dUCB-TCF (relative risk [RR] 0.72, P = .72; RR 0.93, P = .60) but higher after dUCB-other RIC (hazard ratio [HR] 2.70, P = .0001; 1.79 P = .004). Compared with 7 of 8 PBPC transplantations, TRM (but not overall mortality) was lower after dUCB-TCF (RR 0.57, P = .04; RR 0.87 P = .41). The probabilities of survival after dUCB-TCF, dUCB-other RIC, and 8 of 8 PBPC and 7 of 8 PBPC transplantations were 38%, 19%, 44%, and 37%, respectively. With similar survival after 8 of 8, 7 of 8 matched PBPCs, and dUCB-TCF, these data support use of dUCB-TCF transplantation in adults with acute leukemia who may benefit from RIC transplantation urgently or lack a 7-8 of 8 unrelated donor.
Role of the QuantiFERON®-TB Gold In-Tube assay in screening new immigrants for tuberculosis infection
Authors: Mulder Christiaan , van Deutekom Henk , Huisman Erik M. , Toumanian Sophie , Koster Ben F.P.J. , Meijer-Veldman Wieneke , van Loenhout-Rooyackers Joke H. , Appel Milo , Arend Sandra M. , Borgdorff Martien W. , van Leth Frank
Published: April 2012

This study aimed to estimate the risk of progression to active tuberculosis (TB) within 2 yrs after entry in newly arriving immigrants who were screened with the QuantiFERON®-TB Gold In-Tube assay (QFT-GIT; Cellestis, Carnegie, Australia).

In a case–base design, we determined the prevalence QFT-GIT-positive subjects among a representative sample of immigrants aged ≥18 yrs who arrived between April 2009 and March 2011 (the base cohort). Active TB patients (cases) within 2 yrs post-arrival in 2005, 2006 or 2007 were extracted from the Netherlands Tuberculosis Register. The risk of progression to active TB was estimated using Bayesian analyses to adjust for the sensitivity of QFT-GIT.

Among the base cohort, 20% of 1,468 immigrants were QFT-GIT positive. Stratified by TB incidence in the person's country of origin as low (<100 cases per 100,000 population), intermediate (100–199 cases per 100,000) or high (≥200 cases per 100,000), the risk of progression to active TB per 100,000 arriving immigrants if QFT-GIT positive (95% credibility interval) was 456 (95% CI 307–589), 590 (397–762) and 386 (259–499), respectively, compared with 18 (0–46), 38 (0–97) and 28 (0–71) if QFT-GIT negative.

Screening newly arriving immigrants with QFT-GIT contributes to detecting those at high risk of subsequent TB reactivation within 2 yrs after entry, which offers opportunities for prevention by targeted interventions.
Double Y-stenting for tracheobronchial stenosis
Authors: Oki Masahide , Saka Hideo
Published: April 2012

The purpose of the present study was to evaluate the feasibility, efficacy and safety of the double Y-stenting technique, by which silicone Y-stents are placed on both the main carina and another peripheral carina, for patients with tracheobronchial stenosis.

Under general anaesthesia, using rigid and flexible bronchoscopes, a Dumon™ Y-stent (Novatech, La Ciotat, France) was first placed on the primary right or secondary left carina followed by another Y-stent on the main carina so as to insert the bronchial limb of the stent into the first Y-stent. Patients who underwent double Y-stent placement during 3 yrs and 1 month in a single centre were retrospectively reviewed.

In the study period, 93 patients underwent silicone stent placement and 12 (13%) underwent double Y-stent placement (11 for right and one for left bronchus). A combination of Y-stents, 14×10×10 mm and 16×13×13 mm in outer diameter, were most frequently used. Dyspnoea was relieved in all patients. Six out of seven patients with supplemental oxygen before stent placement could be discharged without supplemental oxygen. Median survival after stenting was 94.5 days. One pneumothorax and one granuloma formation occurred.

Double Y-stent placement for patients with tracheobronchial stenosis was technically feasible, effective and acceptably safe.
Wash-out kinetics and efficacy of a modified lavage technique for alveolar proteinosis
Authors: Bonella Francesco , Bauer Peter C. , Griese Matthias , Wessendorf Thomas E. , Guzman Josune , Costabel Ulrich
Published: April 2012

Whole lung lavage (WLL) is the standard treatment for pulmonary alveolar proteinosis (PAP). This study aimed to provide data about the kinetics of the protein wash-out, to identify factors influencing the protein concentration in the recovered fluid and to assess the efficacy of a modified lavage technique.

Samples of 180 WLLs from 42 adult PAP patients were collected. 110 WLLs were performed according to the classical technique. In 70 WLLs, repeated manual ventilation was applied during the procedure. Spectrophotometry was used to measure the protein concentration in the recovered fluid.

The initial protein concentration in the recovered fluid was 460 mg·dL−1, the final concentration was 26 mg·dL−1and the total amount of removed proteins during a lavage was 17.5 g. A history of dust exposure was associated with a higher residual protein concentration in the recovered fluid (p=0.000013). The amount of removed proteins correlated inversely with the diffusing capacity of the lung for carbon monoxide (p=0.001) and oxygen tension (p=0.004). The modified technique removed a greater amount of proteins than the classical technique and prolonged the time to relapse (p=0.011).

Exposure to dust seems to influence the kinetics of the protein wash-out. Applying manual ventilation during the procedure can enhance the efficacy of WLL.
Value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules
Authors: Schwarz Carsten , Schönfeld Nicolas , Bittner Roland C. , Mairinger Thomas , Rüssmann Holger , Bauer Torsten T. , Kaiser Dirk , Loddenkemper Robert
Published: April 2012

The diagnostic value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules (SPN) is still under debate among pneumologists, radiologists and thoracic surgeons.

In a prospective observational manner, flexible bronchoscopy was routinely performed in 225 patients with SPN of unknown origin.

Of the 225 patients, 80.5% had lung cancer, 7.6% had metastasis of an extrapulmonary primary tumour and 12% had benign aetiology. Unsuspected endobronchial involvement was found in 4.4% of all 225 patients (or in 5.5% of patients with lung cancer). In addition, flexible bronchoscopy clarified the underlying aetiology in 41% of the cases. The bronchoscopic biopsy results from the SPN were positive in 84 (46.5%) patients with lung cancer. Surgery was cancelled due to the results of flexible bronchoscopy in four cases (involvement of the right main bronchus (impaired pulmonary function did not allow pneumonectomy) n=1, small cell lung cancer n=1, bacterial pneumonia n=2), and the surgical strategy had to be modified to bilobectomy in one patient.

Flexible bronchoscopy changed the planned surgical approach in five cases substantially. These results suggest that routine flexible bronchoscopy should be included in the regular pre-operative work-up of patients with SPN.
Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis
Authors: Sotgiu Giovanni , Centis Rosella , D'Ambrosio Lia , Alffenaar Jan-William C. , Anger Holly A. , Caminero Jose A. , Castiglia Paolo , De Lorenzo Saverio , Ferrara Giovanni , Koh Won-Jung , Schecter Giesela F. , Shim Tae S. , Singla Rupak , Skrahina Alena , Spanevello Antonio , Udwadia Zarir F. , Villar Miquel , Zampogna Elisabetta , Zellweger Jean-Pierre , Zumla Alimuddin , Migliori Giovanni Battista
Published: April 2012

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis.

12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure).

Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21–90) and 61 (29–119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤600 mgversus>600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg.

The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.
Plumbagin reverses proliferation and resistance to apoptosis in experimental PAH
Authors: Courboulin Audrey , Barrier Marjorie , Perreault Tanya , Bonnet Pierre , Tremblay Veronique L. , Paulin Roxane , Tremblay Ève , Lambert Caroline , Jacob Maria H. , Bonnet Sandra N. , Provencher Steeve , Bonnet Sébastien
Published: April 2012

Like cancer, pulmonary arterial hypertension (PAH) is characterised by a pro-proliferative and anti-apoptotic phenotype. In PAH, pulmonary artery smooth muscle cell (PASMC) proliferation is enhanced and apoptosis suppressed. The sustainability of this phenotype requires the activation of pro-survival transcription factors, such as signal transducer and activator of transcription (STAT)3 and nuclear factor of activated T-cells (NFAT). There are no drugs currently available that are able to efficiently and safely inhibit this axis. We hypothesised that plumbagin (PLB), a natural organic compound known to block STAT3 in cancer cells, would reverse experimental pulmonary hypertension.

Using human PAH-PASMC, we demonstratedin vitrothat PLB inhibits the activation of the STAT3/NFAT axis, increasing the voltage-gated K+current bone morphogenetic protein receptor type II (BMPR2), and decreasing intracellular Ca2+contentration ([Ca2+]i), rho-associated coiled-coil containing protein kinase (ROCK)1 and interleukin (IL)-6, contributing to the inhibition of PAH-PASMC proliferation and resistance to apoptosis (proliferating cell nuclear antigen (PCNA), TUNEL, Ki67 and anexine V).In vivo, PLB oral administration decreases distal pulmonary artery remodelling, mean pulmonary artery pressure and right ventricular hypertrophy without affecting systemic circulation in both monocrotaline- and sugen/chronic hypoxia-induced PAH in rats.

This study demonstrates that the STAT3/NFAT axis can be therapeutically targeted by PLB in human PAH-PASMC and experimental PAH rat models. Thus, PLB could be considered a specific and attractive future therapeutic strategy for PAH.
Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459
Authors: Singh Dave , Cadden Paul , Hunter Michael , Pearce Collins Lisa , Perkins Mike , Pettipher Roy , Townsend Elizabeth , Vinall Shân , O'Connor Brian
Published: April 2012

CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a G-protein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D2-driven chemotaxis. We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients.

A randomised, double-blind, placebo-controlled, two-way crossover study of 16 days’ treatment with OC000459 (200 mg twice daily) on the late (LAR) and early (EAR) asthmatic responses to bronchial allergen challenge was conducted, with 16 subjects completing the study.

There was a 25.4% (95% CI 5.1–45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p=0.018) but no effect on the EAR. Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment (p=0.002). PGD2-induced blood eosinophil shape changeex vivowas assessed at day 7 (n=7). The AUC of eosinophil shift for OC000459 was lower than placebo; the mean difference was -33.6% (95% CI -66.8– -0.4%; p=0.048).

OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils. This CRTH2 antagonist appears to inhibit allergic inflammation in asthma.
Early life lung function and respiratory outcome in the first year of life
Authors: van Putte-Katier Nienke , van der Gugten Anne C. , Uiterwaal Cuno S.P.M. , de Jong Brita M. , Numans Mattijs E. , Kimpen Jan L.L. , Verheij Theo J.M. , van der Ent Cornelis K.
Published: April 2012

Abnormal early life lung function is related to wheezing in childhood; however, data on the association with cough are not available. We determined the relationship between early life lung function and wheeze and cough during the first year of life, adjusted for other possible risk factors.

Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements were performed before the age of 2 months. Information on pre- and perinatal factors, general characteristics and anthropometrics were assessed by questionnaires. Follow-up data on respiratory symptoms were assessed by daily questionnaires.

836 infants had valid lung function measurements and complete follow-up data for respiratory symptoms at 1 yr of age. Multivariable Poisson analysis showed that higher values of respiratory resistance (Rrs) and time constant (τrs) were associated with an increased risk for wheeze and cough during the first year of life. Higher values of respiratory compliance (Crs) were associated with a decreased risk for wheeze and cough.

Rrs,Crsandτrsmeasured shortly after birth were independently associated with wheeze and cough during the first year of life. As the strength of the relationships were different for wheeze and cough, they should be used as two separate entities.
Diagnosis-related deterioration of lung function after extracorporeal membrane oxygenation
Authors: Spoel Marjolein , Laas Roxanne , Gischler Saskia J. , Hop Wim J.C. , Tibboel Dick , de Jongste Johan C. , Ijsselstijn Hanneke
Published: April 2012

The aim of the study was to assess lung function longitudinally after neonatal extracorporeal membrane oxygenation (ECMO), and to identify any effects of diagnosis and perinatal characteristics.

121 neonatal ECMO-treated children (70 with meconium aspiration syndrome, 20 congenital diaphragmatic hernia and 31 with other diagnoses) performed a total of 191 lung function measurements at 5, 8 and/or 12 yrs. We assessed dynamic and static lung volumes, reversibility of airway obstruction and diffusion capacity.

Mean SDS forced expiratory volume in 1 s (FEV1) at 5 yrs before and after bronchodilation (-0.51 and 0.07) was significantly higher than at 8 (-0.79 and -0.4; p<0.04) and 12 yrs (-1.10 and -0.52; p<0.003). Mean SDS for all spirometric parameters before and after bronchodilation were significantly lower in the congenital diaphragmatic hernia group compared with the other diagnostic groups (all p≤0.025). A significant volume of trapped air was observed in 86% patients with congenital diaphragmatic hernia, 50% with meconium aspiration syndrome and 58% with other diagnoses. After bronchodilation, mean SDS FEV1and forced vital capacity were negatively influenced by duration of ventilation (both p<0.001) and duration of ECMO (p=0.003 and p=0.02, respectively).

Long-term pulmonary sequelae after neonatal ECMO-treatment mainly occur in congenital diaphragmatic hernia patients and tend to deteriorate over time.
Decreased cerebrovascular response to CO2in post-menopausal females with COPD: role of oxidative stress
Authors: Hartmann Sara E. , Pialoux Vincent , Leigh Richard , Poulin Marc J.
Published: April 2012

Chronic obstructive pulmonary disease (COPD) is associated with cerebrovascular abnormalities and an overproduction of reactive oxygen species. We hypothesised that COPD patients have oxidant-related cerebrovascular dysfunction. Our main objective was to evaluate cerebrovascular reactivity and its relationship with oxidative stress in females with COPD.

We studied eight females with moderate COPD and 10 healthy female control subjects of similar age. Transcranial Doppler ultrasound assessed cerebral blood flow (CBF) velocity during hypercapnia. Plasma was assessed at rest for DNA oxidation, advanced oxidation protein products, lipid peroxidation, nitrotyrosine, antioxidant enzyme activity (glutathione peroxidase and catalase) and end-products of nitric oxide metabolism.

Moderate COPD patients showed decreased cerebrovascular sensitivity to carbon dioxide (CO2) (COPD 1.17±0.54versuscontrol 2.15±0.73 cm·s−1·mmHg−1; p<0.01). COPD patients had higher levels of DNA and lipid oxidation, advanced oxidation protein products and higher glutathione peroxidase activity (p<0.05). Controlling for measures of oxidative stress (DNA and lipid oxidation, and advanced oxidation protein product) eliminates statistically significant differences between the COPD and control groups in the CBF sensitivity to CO2.

Females with moderate COPD were found to have cerebrovascular dysfunction. Our results suggest that increased levels of systemic oxidative stress may have implications in the cerebrovascular dysfunction observed during hypercapnia in COPD.
Domestic use of cleaning sprays and asthma activity in females
Authors: Le Moual Nicole , Varraso Raphaelle , Siroux Valérie , Dumas Orianne , Nadif Rachel , Pin Isabelle , Zock Jan-Paul , Kauffmann Francine
Published: April 2012

We aimed to study the associations between the household use of cleaning sprays and asthma symptoms and control of asthma, in females from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA).

Data were available for 683 females (mean age 44 yrs, 55% never smokers, 439 without asthma and 244 with current asthma). Both domestic exposures and asthma phenotypes (asthma symptom score, current asthma, poorly-controlled asthma (56%)) were evaluated as previously described in the European Community Respiratory Health Survey. Associations between the use of sprays and asthma phenotypes were evaluated using logistic and nominal regressions, adjusted for age, smoking, body mass index and occupational exposures.

Significant associations were observed between the weekly use of at least two types of sprays and a high asthma symptom score (OR (95% CI) 2.50 (1.54–4.03)) compared with a null score. Consistent results were observed for current asthma (1.67 (1.08–2.56)) and poorly-controlled asthma (2.05 (1.25–3.35)) compared with females without asthma. The association for current asthma was higher in females not reporting avoidance of polluted places (2.12 (1.27–3.54)) than in those reporting such avoidance (0.99 (0.53–1.85)).

The common use of household cleaning sprays is positively associated with a high asthma symptom score, current asthma and poorly-controlled asthma in females.
Emerging anti-inflammatory strategies for COPD
Authors: Cazzola Mario , Page Clive P. , Calzetta Luigino , Matera M. Gabriella
Published: April 2012

The hallmark of chronic obstructive pulmonary disease (COPD) is an enhanced or abnormal inflammatory immune response of the lungs to inhaled particles and gases, usually from cigarette smoke, characterised by increased numbers of neutrophils, activated macrophages and activated T-lymphocytes (Tc1 and Th1 cells). Therefore, suppression of the inflammatory response is a logical approach to the treatment of COPD. Despite the inflammatory nature of COPD, currently available anti-inflammatory therapies provide little or no benefit in COPD patients and may have detrimental effects. For this reason, there is an urgent need to discover effective and safe anti-inflammatory treatments that might prevent the relentless progression of the disease. In recent years, attention has largely been focused on inhibition of recruitment and activation of inflammatory cells, and on antagonism of their products. In this review, we put together a summary of the state-of-the-art development of clearly and/or potentially useful anti-inflammatory strategies in COPD.
Is it time for home treatment of pulmonary embolism?
Authors: Lankeit Mareike , Konstantinides Stavros
Published: April 2012

Acute pulmonary embolism (PE) is a frequent cause of death, but not all patients are at high risk of an adverse early outcome. It has been proposed that selected patients may be considered for early discharge and home treatment, but it was only recently that improved risk assessment strategies permitted advances in the identification of low-risk PE.

Clinical prediction rules, such as the Pulmonary Embolism Severity Index (PESI), and laboratory biomarkers, particularly natriuretic peptides and cardiac troponins, appeared capable of excluding severe PE and serious comorbidity.

Recently, two randomised trials and two prospective cohort studies investigated the feasibility and safety of outpatient treatment. All excluded patients with haemodynamic instability and serious comorbidity, but only one trial used a validated clinical score (PESI) for patient inclusion, and only one cohort study employed a biomarker test. Overall, 90-day outcome was favourable and the results appear promising.

To optimise patient selection, future trials will need to test simplified clinical scores combined with high-sensitivity biomarker assays, and it will have to be determined whether echocardiography and/or compression ultrasonography are also required before discharge. Furthermore, ongoing trials will show whether new oral anticoagulants are a safe and cost-effective option for managing patients out of hospital.
Distribution patterns of influenza virus receptors and viral attachment patterns in the respiratory and intestinal tracts of seven avian species
Authors: Costa Taiana , Chaves Aida J , Valle Rosa , Darji Ayub , van Riel Debby , Kuiken Thijs , Majó Natàlia , Ramis Antonio
Published: April 2012

This study assessed the presence of sialic acid α-2,3 and α-2,6 linked glycan receptors in seven avian species. The respiratory and intestinal tracts of the chicken, common quail, red-legged partridge, turkey, golden pheasant, ostrich, and mallard were tested by means of lectin histochemistry, using the lectins Maackia amurensis agglutinin II and Sambucus nigra agglutinin, which show affinity for α-2,3 and α-2,6 receptors, respectively. Additionally, the pattern of virus attachment (PVA) was evaluated with virus histochemistry, using an avian-origin H4N5 virus and a human-origin seasonal H1N1 virus. There was a great variation of receptor distribution among the tissues and avian species studied. Both α-2,3 and α-2,6 receptors were present in the respiratory and intestinal tracts of the chicken, common quail, red-legged partridge, turkey, and golden pheasant. In ostriches, the expression of the receptor was basically restricted to α-2,3 in both the respiratory and intestinal tracts and in mallards the α-2,6 receptors were absent from the intestinal tract. The results obtained with the lectin histochemistry were, in general, in agreement with the PVA. The differential expression and distribution of α-2,3 and α-2,6 receptors among various avian species might reflect a potentially decisive factor in the emergence of new viral strains.
Consumers' experiences and values in conventional and alternative medicine paradigms: a problem detection study (PDS)
Authors: Emmerton Lynne , Fejzic Jasmina , Tett Susan E
Published: April 2012

Background

This study explored consumer perceptions of complementary and alternative medicine (CAM) and relationships with CAM and conventional medicine practitioners.

A problem detection study (PDS) was used. The qualitative component to develop the questionnaire used a CAM consumer focus group to explore conventional and CAM paradigms in healthcare. 32 key issues, seven main themes, informed the questionnaire (the quantitative PDS component - 36 statements explored using five-point Likert scales.)

Results

Of 300 questionnaires distributed (Brisbane, Australia), 83 consumers responded. Results indicated that consumers felt empowered by using CAM and they reported positive relationships with CAM practitioners. The perception was that CAM were used most effectively as long-term therapy (63% agreement), but that conventional medicines would be the best choice for emergency treatment (81% agreement). A majority (65%) reported that doctors appeared uncomfortable about consumers' visits to CAM practitioners. Most consumers (72%) believed that relationships with and between health practitioners could be enhanced by improved communication. It was agreed that information sharing between consumers and healthcare practitioners is important, and reported that "enough" information is shared between CAM practitioners and consumers. Consumers felt comfortable discussing their medicines with pharmacists, general practitioners and CAM practitioners, but felt most comfortable with their CAM practitioners.

Conclusions

This PDS has emphasized the perceived importance of open communication between consumers, CAM and conventional providers, and has exposed areas where CAM consumers perceive that issues exist across the CAM and conventional medicine paradigms. There is a lot of information which is perceived as not being shared at present and there are issues of discomfort and distrust which require resolution to develop concordant relationships in healthcare. Further research should be based on optimisation of information sharing, spanning both conventional and CAM fields of healthcare, due to both the relevance of concordance principles within CAM modalities and the widespread use of CAM by consumers.
The pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestation in Ethiopia: a retrospective study
Authors: Berhe Tesfaye , Melkamu Yilma , Amare Amanuel
Published: April 2012

Background

Even though the prevalence of HIV infection among the adult population in Ethiopia was estimated to be 2.2% in 2008, the studies on the pattern of neurological manifestations are rare. The aim of this retrospective study was to assess the pattern and predictors of mortality of HIV/AIDS patients with neurologic manifestations.

Methods

Medical records of 347 patients (age ≥13 years) admitted to Tikur Anbesa Hospital from September 2002 to August 2009 were reviewed and demographic and clinical data were collected.

Results

Data from 347 patients were analysed. The mean age was 34.6 years. The diagnosis of HIV was made before current admission in 33.7% and 15.6% were on antiretroviral therapy (ART). Causes of neurological manifestation were: cerebral toxoplasmosis (36.6%), tuberculous meningitis (22.5%), cryptococcal meningitis (22.2%) and bacterial meningitis (6.9%). HIV-encephalopathy, primary central nervous system (CNS) lymphoma and progressive multifocal leukoencephalopathy were rare in our patients. CD4 count was done in 64.6% and 89.7% had count below 200/mm3[mean = 95.8, median = 57] and 95.7% were stage IV. Neuroimaging was done in 38% and 56.8% had mass lesion. The overall mortality was 45% and the case-fatality rates were: tuberculous meningitis (53.8%), cryptococcal meningitis (48.1%), cerebral toxoplasmosiss (44.1%) and bacterial meningitis (33.3%). Change in sensorium and seizure were predictors of mortality.

Conclusions

CNS opportunistic infections were the major causes of neurological manifestations of HIV/AIDS and were associated with high mortality and morbidity. Almost all patients had advanced HIV disease at presentation. Early diagnosis of HIV, prophylaxis and treatment of opportunistic infections, timely ART, and improving laboratory services are recommended. Mortality was related to change in sensorium and seizure.
Induction of superficial zone protein (SZP)/lubricin/PRG 4 in muscle-derived mesenchymal stem/progenitor cells by transforming growth factor-β1 and bone morphogenetic protein-7
Authors: Andrades José A , Motaung Shirley C , Jiménez-Palomo Pedro , Claros Silvia , López-Puerta José M , Becerra José , Schmid Thomas M , Reddi A Hari
Published: April 2012

Introduction

Articular cartilage (AC) is an avascular tissue with precise polarity and organization. The three distinct zones are: surface, middle and deep. The production and accumulation of the superficial zone protein (SZP), also known as lubricin, by the surface zone is a characteristic feature of AC. To date, there is a wealth of evidence showing differentiation of AC from mesenchymal stem cells. Most studies that described chondrogenic differentiation did not focus on AC with characteristic surface marker SZP/lubricin. The present investigation was initiated to determine the induction of SZP/lubricin in skeletal muscle-derived mesenchymal stem/progenitor cells (MDMSCs) by transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7).

Methods

MDMSCs were cultured as a monolayer at a density of 1 × 105 cells/well in 12-well tissue culture plates. Cell cultures were treated for 3, 7 and 10 days with TGF-β1 and BMP-7. The medium was analyzed for SZP. The cells were used to isolate RNA for RT-PCR assays for SZP expression.

Results

The SZP/lubricin increased in a time-dependent manner on Days 3, 7 and 10 in the medium. As early as Day 3, there was a three-fold increase in response to 3 ng/ml of TGF-β1 and 300 ng/ml of BMP-7. This was confirmed by immunochemical localization of SZP as early as Day 3 after treatment with TGF-β1. The expression of SZP mRNA was enhanced by TGF-β1.

Conclusions

The present investigation demonstrated the efficient and reproducible induction of SZP/lubricin accumulation by TGF-β1 and BMP-7 in skeletal MDMSCs. Optimization of the experimental conditions may permit the utility of MDMSCs in generating surface zone-like cells with phenotypic markers of AC and, therefore, constitute a promising cell source for tissue engineering approaches of superficial zone cartilage.
Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)
Authors: Fagin Ursula , Pitann Silke , Gross Wolfgang L , Lamprecht Peter
Published: April 2012

Introduction

Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polarization.

Methods

Multicolor flow cytometry was used to analyze CCR4, CCR6, and intracellular cytokine expression of T cells from whole blood of GPA-patients (n = 26) and healthy controls (n = 20). CCR7 and CD45RA were included for phenotypic characterization.

Results

We found a significant increase in the percentages of circulating CCR4+ and CCR6+ cells within the total CD4+ T cell population in GPA. In contrast, there was no difference in the percentages of CD8+CCR4+ and CD8+CCR6+ T cells between GPA and healthy controls. CCR4 and CCR6 expression was largely confined to central (TCM) and effector memory T cells (TEM, TEMRA). A significant increase in the frequency of CCR4+ and CCR6+ TEMRA and CCR6+ TCM was shown in GPA. Of note, we could dissect CCR4 and CCR6 expressing CCR7+CD45RAmed very early memory T cells (TVEM) from genuine CCR7+CD45RAhigh naïve T cells lacking CCR4 and CCR6 expression for peripheral tissue-migration within the CCR7+CD45RA+ compartment. The frequencies of CCR4+ and CCR6+ TVEM were also significantly increased in GPA. An increased percentage of IL-17+ and IL-22+ cells was detected in the CCR6+ cell subsets and IL-4+ cells in the CRR4+ cell subset when compared with CD4+ cells lacking CCR4 and CCR6 expression.

Conclusions

Increased frequencies of circulating CCR4+ and CCR6+ memory T cell subsets including hitherto unreported TVEM suggest persistent T cell activation with the accumulation of CCR4+ and CCR6+ cells in GPA. CCR4 and CCR6 could be involved in the recruitment of T cells including cytokine-producing subsets to inflamed sites in GPA.
Immune regulation of Rab proteins expression and intracellular transport
Authors: Pei Gang , Bronietzki Marc , Gutierrez Maximiliano Gabriel
Published: April 2012

Review on the immune signals that regulate Rab protein expression and transport, and the consequences during the immune response.

Compartmentalization in cells of the immune system, the focus of this review, facilitates the spatiotemporal organization of cellular responses essential for specialized immune functions. In this process of compartment maintenance, Rab proteins are central regulators of protein-mediated transport and fusion of intracellular structures. It is widely believed that the intracellular concentration of proteins that regulate intracellular transport, including Rab proteins, is constitutively mantained. However, there is a growing body of evidence indicating that transcriptional rates of Rab proteins can be modified. This process is especially evident during immune activation and argues that after activation, these cells require higher levels of Rab proteins. The aim of this review is to discuss evidence showing the increasing links between Rab protein expression and intracellular transport, particularly in monocytes and macrophages. We highlight here biological processes in which the expression of Rab GTPases is selectively regulated, leading to the activation of specific intracellular routes. Further, we focus on the immune regulation of intracellular transport after cytokine activation and microbial infection, with an emphasis in mycobacterial infection.