bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical effects of a nine-month web-based intervention in subacute non-specific low back pain patients: a randomized controlled trial
Authors: del Pozo-Cruz Borja , Gusi Narcis , del Pozo-Cruz Jesús , Adsuar Jose C , Hernandez-Mocholí Miguel , Parraca Jose A 
Published: June 2012

Objective: To test the clinical effect of a web-based lower back pain intervention on quality of life and selected lower back pain outcomes. Design: A prospective single-blinded randomized intervention. Setting: Occupational preventive service. Subjects: One hundred office workers with non-specific subacute lower back pain. Intervention: The 50 intervention group subjects were educated daily about sitting correctly and asked to perform exercises shown by video demonstrations on the university website. The exercise routines included strengthening, mobility and stretching exercises focused on the postural stability muscles. The 50 control group subjects only received standard occupational care. Measures: Outcomes were measured by the EuroQol questionnaire five dimensions three levels, the Oswestry Disability Index, and the StarT Back Screening Tool questionnaires. At nine months, the intervention group outcomes were compared to the baseline data and the control group outcomes. Results: For 97% ( n = 45) of the experimental group quality of life (clinical utility) improved significantly; 3.58 times greater than the control group. Oswestry Disability Index showed an odds ratio (OR) of 5.42 with a 37% ( n = 17) change for the intervention group with respect to the control group. With regard to the StarT Back Screening Tool, 76% ( n = 35) of the intervention group improved their clinical state (odds ratio = 3.04 with respect to the control group improvement). Logistic regression analysis revealed positive changes in EuroQol questionnaire, increasing the likelihood of observing positive changes in StarT Back Screening Tool (OR = 15.5) and Oswestry Disability Index (OR = 4.5). Conclusions: The intervention showed clinical improvements in quality of life and selected lower back pain outcomes in the experimental group compared to the control group.
Effects of repetitive transcranial magnetic stimulation on somatosensory evoked potentials and high frequency oscillations in migraine
Authors: Coppola Gianluca , De Pasqua Victor , Pierelli Francesco , Schoenen Jean 
Published: June 2012

Background: In previous studies we found that high-frequency somatosensory oscillations (HFOs) reflecting thalamo-cortical activation were decreased in migraineurs between attacks and that high-frequency repetitive transcranial magnetic stimulation (rTMS) was able to normalize the habituation deficit of visual evoked potentials (VEPs). Here we study the effects of activating (10 Hz) or inhibiting (1 Hz) rTMS on conventional low-frequency (LF) and high-frequency somatosensory evoked potentials (SSEPs). Subjects and methods: rTMS was applied on the motor cortex of 13 healthy volunteers (HVs) and 13 migraine without aura (MO) patients. We measured N20-P25 LF-SSEP amplitude and habituation, and maximal peak-to-peak amplitude of early and late HFOs before and after rTMS. Results: In HVs, 1 Hz rTMS significantly reduced the amplitude of the first LF-SSEP block and its habituation. In MO patients, 10 Hz rTMS increased the amplitude of the first block and induced habituation. Ten Hz rTMS produced an increase of late HFO in both groups, but more interestingly, in MO patients also significantly increased the early HFOs, which are reduced at baseline compared to those of HVs. Conclusions: These data confirm for SSEP that excitatory rTMS can normalize habituation in migraine patients and show that this is accompanied by early an HFO increase, which is thought to reflect thalamo-cortical activity. Taken together with similar effects we observed for VEPs, this finding supports the hypothesis that dysfunctioning thalamo-cortical loops may be responsible for the interictal habituation deficit in migraine.
Chronic pain as a narratological distress: a phenomenological study
Authors: Lavie-Ajayi Maya , Almog Nitsan , Krumer-Nevo Michal 
Published: June 2012

Objectives: This paper reports finding from a study that focused on people living with chronic pain, chronicling their experiences of pain and emotional distress, and their social and personal narratives. Methods: The paper presents an interpretative phenomenological analysis (IPA) of six interviews conducted with men and women aged between 27 and 61. The interviews were taken from a larger study of the experience of chronic pain. Findings: Chronic pain is a double faced phenomenon: a vivid and total experience on one hand, an elusive and deceptive phenomenon on the other. The nature of this phenomenon – together with the medical and public discourse that ignores and delegitimizes chronic pain this condition – prompts people to question their own experiences and to face what we define as a narratological distress. Discussion: Narratological distress is the internal battle between two unwanted narratives: The elusive delegitimizing narrative of denial, which seeks to ignore the experience of pain; and the narrative that acknowledges the pain, but with the price of accepting oneself as “ill” or “disabled.”
Protein disulfide isomerase capture during thrombus formation in vivo depends on the presence of β3 integrins
Authors: Cho Jaehyung , Kennedy Daniel R. , Lin Lin , Huang Mingdong , Merrill-Skoloff Glenn , Furie Barbara C. , Furie Bruce 
Published: June 2012

AbstractExtracellular protein disulfide isomerase (PDI) is required for platelet thrombus formation and fibrin generation after arteriolar wall injury in live mice. PDI is secreted from platelets and endothelial cells on cellular activation, but the mechanism of capture of secreted PDI within the injured vasculature is unknown. We establish that, like the endothelial β3 integrin αVβ3, the platelet integrin αIIbβ3 binds PDI. PDI also binds to recombinant β3. Using intravital microscopy, we demonstrate that PDI accumulation at the site of laser-induced arteriolar wall injury is markedly reduced in β3-null (β3−/−) mice, and neither a platelet thrombus nor fibrin is generated at the vessel injury site. The absence of fibrin after vascular injury in β3−/− mice is because of the absence of extracellular PDI. To evaluate the relative importance of endothelial αVβ3 versus platelet αIIbβ3 or αVβ3, we performed reciprocal bone marrow transplants on wild-type and β3−/− mice. PDI accumulation and platelet thrombus formation were markedly decreased after vessel injury in wild-type mice transplanted with β3−/− bone marrow or in β3−/− mice transplanted with wild-type bone marrow. These results indicate that both endothelial and platelet β3 integrins contribute to extracellular PDI binding at the vascular injury site.
FANCL ubiquitinates β-catenin and enhances its nuclear function
Authors: Dao Kim-Hien T. , Rotelli Michael D. , Petersen Curtis L. , Kaech Stefanie , Nelson Whitney D. , Yates Jane E. , Hanlon Newell Amy E. , Olson Susan B. , Druker Brian J. , Bagby Grover C. 
Published: June 2012

Abstract
Bone marrow failure is a nearly universal complication of Fanconi anemia. The proteins encoded by FANC genes are involved in DNA damage responses through the formation of a multisubunit nuclear complex that facilitates the E3 ubiquitin ligase activity of FANCL. However, it is not known whether loss of E3 ubiquitin ligase activity accounts for the hematopoietic stem cell defects characteristic of Fanconi anemia. Here we provide evidence that FANCL increases the activity and expression of β-catenin, a key pluripotency factor in hematopoietic stem cells. We show that FANCL ubiquitinates β-catenin with atypical ubiquitin chain extension known to have nonproteolytic functions. Specifically, β-catenin modified with lysine-11 ubiquitin chain extension efficiently activates a lymphocyte enhancer-binding factor-T cell factor reporter. We also show that FANCL-deficient cells display diminished capacity to activate β-catenin leading to reduced transcription of Wnt-responsive targets c-Myc and Cyclin D1. Suppression of FANCL expression in normal human CD34+ stem and progenitor cells results in fewer β-catenin active cells and inhibits expansion of multilineage progenitors. Together, these results suggest that diminished Wnt/β-catenin signaling may be an underlying molecular defect in FANCL-deficient hematopoietic stem cells leading to their accelerated loss.
General and abdominal obesity and incident asthma in adults: the HUNT study
Authors: Brumpton Ben , Langhammer Arnulf , Romundstad Pål , Chen Yue , Mai Xiao-Mei 
Published: June 2012

Measures of body mass index (BMI) and waist circumference define general obesity and abdominal obesity respectively. While high BMI has been established as a risk factor for asthma in adults, waist circumference has seldom been investigated.To determine the association between BMI, waist circumference and incident asthma in adults, we conducted a prospective study (n=23,245) in a population living in Nord-Trøndelag, Norway in 1995–2008.Baseline BMI and waist circumference were measured and categorised as general obesity (BMI ≥30.0 kg·m2) and abdominal obesity (waist circumference ≥88 cm in females and ≥102 cm in males). Incident asthma was self-reported new-onset cases during an 11-yr follow-up period. Odds ratios for asthma associated with obesity were calculated using multivariable logistic regression.General obesity was a risk factor for asthma in females (OR 1.96, 95% CI 1.52–2.52) and males (OR 1.84, 95% CI 1.30–2.59). In females, after additional adjustment for BMI, abdominal obesity remained a risk factor for asthma development (OR 1.46, 95% CI 1.04–2.05). Abdominal obesity seems to increase the risk of incident asthma in females in addition to BMI, indicating that using both measures of BMI and waist circumference in females may be a superior clinical assessment for asthma risk than any measure alone.
Lung function from infancy to preschool in a cohort of children with cystic fibrosis
Authors: Brumback Lyndia C. , Davis Stephanie D. , Kerby Gwendolyn S. , Kloster Margaret , Johnson Robin , Castile Robert , Hiatt Peter W. , Hart Meeghan , Rosenfeld Margaret 
Published: June 2012

This study aimed to describe lung function in a cohort of children with cystic fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool spirometry.Children performed up to four IPFTs (raised volume rapid thoracic compression technique) over 1 yr and five preschool spirometry tests over up to 2 yrs during participation in prospective, multicentre studies of infant and preschool lung function. All lung function data were reviewed centrally for measurement acceptability.45 children had 252 acceptable measurements (137 IPFTs and 115 preschool spirometries) at ages 0.3–6.5 yrs. The median number of measurements per participant was 6 (range 3–9). RecentPseudomonas aeruginosainfection was associated with 5.1% (95% CI 0.01–9.9%) lower forced expiratory volume in 0.5 s (FEV0.5) and 16.4% (95% CI 7.0–24.9%) lower forced expiratory flow at 25–25% of forced vital capacity (FEF25–75%), after adjustment for length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1–10.1%) lower FEV0.5and 10.1% (95% CI 0.6–18.7%) lower FEF25–75%. Even after accounting for infection status, cough, sex, length, test type and centre, there was significant inter-individual variability in lung function (p<0.01 for each of FEV0.5, FEF25–75%and forced vital capacity).RecentP. aeruginosainfection and cough are associated with lower lung function in children with CF. Significant inter-individual variability in lung function remains to be explained.
Protecting the tuberculosis drug pipeline: stating the case for the rational use of fluoroquinolones
Authors: Migliori Giovanni Battista , Langendam Miranda W. , D'Ambrosio Lia , Centis Rosella , Blasi Francesco , Huitric Emma , Manissero Davide , van der Werf Marieke J. 
Published: June 2012

The use of fluoroquinolones (FQs) to treat lower respiratory tract infections (LTRI) other than tuberculosis (TB) allows selection of FQ-resistant TB when TB is misdiagnosed. This study maps national guidelines on the use of FQs for LRTI in Europe and determines the risk of FQ-resistant TB upon FQ treatment before TB diagnosis.A questionnaire was developed to map existing national LRTI and community-acquired pneumonia (CAP) guidelines. A systematic review and meta-analysis were performed to determine the risk of FQ-resistant TB if prescribed FQs prior to TB diagnosis.15 (80%) out of 24 responding European Respiratory Society national delegates reported having national LRTI management guidelines, seven including recommendations on FQ use and one recommending FQs as the first-choice drug. 18 out of 24 countries had national CAP management guidelines, two recommending FQ as the drug of choice. Six studies investigating FQ exposure and the risk of FQ-resistant TB were analysed. TB patients had a three-fold higher risk of having FQ-resistant TB when prescribed FQs before TB diagnosis, compared to non FQ-exposed patients (OR 2.81, 95% CI 1.47–5.39).Although the majority of European countries hold national LRTI/CAP guidelines, our results suggest that a risk of developing FQ resistance exists. Further strengthening of, and adherence to, guidelines is needed to ensure rational use of FQs.
Efficacy, safety and pharmacokinetics of bosentan in portopulmonary hypertension
Authors: Savale Laurent , Magnier Romain , Le Pavec Jérôme , Jaïs Xavier , Montani David , O'Callaghan Dermot S. , Humbert Marc , Dingemanse Jasper , Simonneau Gérald , Sitbon Olivier 
Published: June 2012

Data on treatment of patients with portopulmonary hypertension (PoPH) are limited, as they are usually excluded from randomised controlled trials with pulmonary arterial hypertension (PAH)-specific therapies. This study investigated the short- and long-term efficacy/safety of bosentan in these patients, as well as its pharmacokinetics.All 34 consecutive patients with PoPH treated with first-line bosentan (December 2002 to July 2009) were retrospectively evaluated. Assessments included the New York Heart Association functional class (NYHA FC), blood tests, haemodynamics, 6-min walk distance (6MWD) and event-free status. The pharmacokinetics of bosentan in five patients with Child–Pugh (C-P) class B cirrhosis were compared with idiopathic PAH patients.Significant improvements from baseline were observed in NYHA FC, 6MWD and haemodynamics, and were largely maintained during follow-up. Patients with C-P class B cirrhosis (n=9) had significantly larger haemodynamic improvement after mean±sd5±2 months. Mean follow-up time was 43±19 months; four patients died and seven patients had significant elevation of liver enzymes (annual rate 5.5%). Plasma concentrations of bosentan were higher in patients with C-P class B cirrhosis than those observed in idiopathic PAH.These data confirm the benefit of bosentan treatment for patients with PoPH. Haemodynamic improvements were particularly pronounced in patients with more severe cirrhosis. The safety profile of bosentan was consistent with previous studies.
PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis
Authors: Stephen Jancy , Delvecchio Chris , Spitale Naomi , Giesler Amanda , Radford Katherine , Bilan Pat , Cox P. Gerard , Capone John P. , Nair Parameswaran 
Published: June 2012

Airway smooth muscle cells produce extracellular matrix proteins, which in turn can promote smooth muscle survival, proliferation and migration. Currently available therapies have little effect on airway smooth muscle matrix production and migration. Peroxisome proliferator-activated receptor (PPAR) ligands are reported to decrease migration and matrix production in various cell lines. In this study, we examined the effect of PPAR ligands on human airway smooth muscle (HASM) matrix production and migration.PPAR expression was examined by RT-PCR and Western blotting. Endogenous PPAR activity was examined by transfecting cells with a PPAR response element–luciferase reporter plasmid.We observed that HASM cells express PPARα, β and γ. A six-fold induction of luciferase activity was observed by stimulating cells with a pan-agonist, indicating endogenous PPAR activity. The PPAR ligands ciglitazone, 15-deoxy-Δ12,14-prostaglandin J2and WY-14643 decreased migration towards platelet-derived growth factor receptor. This was not mediated by inhibiting Akt phosphorylation or promoting PTEN activity, but partly through cyclooxygenase-2 induction and prostaglandin E2production that increased cyclic AMP levels in the cells. All three ligands also caused an inhibition of collagen and fibronectin secretion by cultured smooth muscle cells.We conclude that PPAR ligands decrease HASM migration and matrix production and are, therefore, potentially useful for modulating airway remodelling.
TLR9- and Src-dependent expression of Krueppel-like factor 4 controls interleukin-10 expression in pneumonia
Authors: Zahlten Janine , Steinicke Robert , Bertrams Wilhelm , Hocke Andreas C. , Scharf Stefanie , Schmeck Bernd , Witzenrath Martin , Hammerschmidt Sven , Suttorp Norbert , Hippenstiel Stefan 
Published: June 2012

The release of potent pro-inflammatory mediators is crucial to mounting an efficient host response during infection. However, excessive inflammation may lead to deleterious tissue damage. This is highlighted in severe pneumococcal pneumonia, in which the delicate balance between a robust inflammatory response necessary to kill pneumococci and the loss of organ function determines the outcome of the disease.We assessed the regulation of the potent anti-inflammatory cytokine interleukin (IL)-10 in pneumococcal infectionviaWestern blot, ELISA and chromatin immunoprecipitation analysis.Streptococcus pneumoniaeinduced IL-10 expression in mouse lungs and human lung epithelial cells. Pneumococcal infection resulted in a strong induction of Krueppel-like factor (KLF)4 expressionin vivoandin vitro. The induction of both IL-10 and KLF4 is mediated by a pathway involving bacterial DNA, Toll-like receptor (TLR)9, MyD88 and Src kinase. KLF4 is recruited to theil10promoter, and small-interfering RNA-mediated knockdown of KLF4 expression blocked IL-10 expression during pneumococcal infection.In conclusion, KLF4 is induced in a bacterial DNA–TLR9–Src-dependent manner and regulates IL-10 expression, linking the detection of bacterial DNA by TLR9 to the control of an inflammatory response.
Home mechanical ventilation in Australia and New Zealand
Authors: Garner Daniel J. , Berlowitz David J. , Douglas James , Harkness Nick , Howard Mark , McArdle Nigel , Naughton Matthew T. , Neill Alister , Piper Amanda , Yeo Aeneas , Young Alan 
Published: June 2012

This study aims to describe the pattern of home mechanical ventilation (HMV) usage in Australia and New Zealand.34 centres providing HMV in the region were identified and asked to complete a questionnaire regarding centre demographics, patient diagnoses, HMV equipment and settings, staffing levels and methods employed to implement and follow-up therapy.28 (82%) centres responded, providing data on 2,725 patients. The minimum prevalence of HMV usage was 9.9 patients per 100,000 population in Australia and 12.0 patients per 100,000 population in New Zealand. Variation existed across Australian states (range 4–13 patients per 100,000 population) correlating with population density (r=0.82; p<0.05). The commonest indications for treatment were obesity hypoventilation syndrome (OHS) (31%) and neuromuscular disease (NMD) (30%). OHS was more likely to be treated in New Zealand, in smaller, newer centres, whilst NMD was more likely to be treated in Australia, in larger, older centres. Chronic obstructive pulmonary disease was an uncommon indication (8.0%). No consensus on indications for commencing treatment was found.In conclusion, the prevalence of HMV usage varies across Australia and New Zealand according to centre location, size and experience. These findings can assist HMV service planning locally and highlight trends in usage that may be relevant in other countries.
A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations
Authors: Singh Dave , Kampschulte Jorg , Wedzicha Jadwiga A. , Jones Paul W. , Cohuet Géraldine , Corradi Massimo , Higenbottam Tim , Petruzzelli Stefano , Vestbo Jørgen 
Published: June 2012

Combination inhalers containing corticosteroids and long-acting β-agonists are used to reduce exacerbation rates in patients with severe chronic obstructive pulmonary disease (COPD).The FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The traditional physician diagnosis of exacerbations is a co-primary outcome, and the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting patient-reported outcome data are also being used to enhance the detection of exacerbation events. EXACT data are being collected using a novel application of a digital platform technology.FORWARD is therefore expected to provide information on the ability of EXACT to detect and measure exacerbations in a large clinical trial setting. The study design of FORWARD is described in this article.
An earlier and more confident diagnosis of idiopathic pulmonary fibrosis
Authors: du Bois Roland M. 
Published: June 2012

A diagnosis of idiopathic pulmonary fibrosis (IPF) has serious implications for the affected individuals, who have a 50% likelihood of dying within 2−3 yrs, an outcome which is worse than many cancers. A swift and accurate diagnosis is imperative, especially as commencing treatment at a relatively early disease stage may have the greatest impact on reducing disease progression.The 2011, IPF guidelines provide updated and simplified IPF diagnostic criteria that may facilitate making a more confident diagnosis. The key investigational tool is high-resolution computed tomography (HRCT). In the presence of the four classical features, that together accurately identify a usual interstitial pneumonia (UIP) pattern, a definitive diagnosis of IPF can be made. When HRCT honeycombing is absent, even in the presence of all other features including traction bronchiectasis, the guidelines provide no designation for this constellation of features that many clinicians and radiologists would regard as consistent with UIP.The diagnostic algorithm suggested by the 2011 guidelines emphasises the importance of multidisciplinary discussion between clinicians, radiologists and pathologists to improve diagnostic confidence. The course of disease in IPF is unpredictable, but the importance of an early diagnosis is clear, as individuals with less severe lung function abnormalities have a better prognosis.