The main rhinovirus respiratory tract adhesion site (ICAM-1) is upregulated in smokers and patients with chronic airflow limitation (CAL).

BACKGROUND: ICAM-1 is a major receptor for ~60% of human rhinoviruses, and non-typeable Haemophilus influenzae, two major pathogens in COPD. Increased cell-surface expression of ICAM-1 in response to tobacco smoke exposure has been suggested. We have investigated epithelial ICAM-1 expression in both the large and small airways, and lung parenchyma in smoking-related chronic airflow limitation (CAL) patients. METHODS: We evaluated epithelial ICAM-1 expression in resected lung tissue: 8 smokers with normal spirometry (NLFS); 29 CAL patients (10 small-airway disease; 9 COPD-smokers; 10 COPD ex-smokers); Controls (NC): 15 normal airway/lung tissues. Immunostaining with anti-ICAM-1 monoclonal antibody was quantified with computerized image analysis. The percent and type of cells expressing ICAM-1 in large and small airway epithelium and parenchyma were enumerated, plus percentage of epithelial goblet and submucosal glands positive for ICAM- 1. RESULTS: A major increase in ICAM-1 expression in epithelial cells was found in both large (p < 0.006) and small airways (p < 0.004) of CAL subjects compared to NC, with NLFS being intermediate. In the CAL group, both basal and luminal areas stained heavily for ICAM-1, so did goblet cells and sub-mucosal glands, however in either NC or NLFS subjects, only epithelial cell luminal surfaces stained. ICAM-1 expression on alveolar pneumocytes (mainly type II) was slightly increased in CAL and NLFS (p < 0.01). Pack-years of smoking correlated with ICAM-1 expression (r = 0.49; p < 0.03). CONCLUSION: Airway ICAM-1 expression is markedly upregulated in CAL group, which could be crucial in rhinoviral and NTHi infections. The parenchymal ICAM-1 is affected by smoking, with no further enhancement in CAL subjects

β-catenin, Twist and Snail: Transcriptional regulation of EMT in smokers and COPD, and relation to airflow obstruction.

COPD is characterised by poorly reversible airflow obstruction usually due to cigarette smoking. The transcription factor clusters of β-catenin/Snail1/Twist has been implicated in the process of epithelial mesenchymal transition (EMT), an intermediate between smoking and airway fibrosis, and indeed lung cancer. We have investigated expression of these transcription factors and their "cellular localization" in bronchoscopic airway biopsies from patients with COPD, and in smoking and non-smoking controls. An immune-histochemical study compared cellular protein expression of β-catenin, Snail1 and Twist, in these subject groups in 3 large airways compartment: epithelium (basal region), reticular basement membrane (Rbm) and underlying lamina propria (LP). β-catenin and Snail1 expression was generally high in all subjects throughout the airway wall with marked cytoplasmic to nuclear shift in COPD (P < 0.01). Twist expression was generalised in the epithelium in normal but become more basal and nuclear with smoking (P < 0.05). In addition, β-catenin and Snail1 expression, and to lesser extent of Twist, was related to airflow obstruction and to expression of a canonical EMT biomarker (S100A4). The β-catenin-Snail1-Twist transcription factor cluster is up-regulated and nuclear translocated in smokers and COPD, and their expression is closely related to both EMT activity and airway obstruction

Pulmonary valve stenosis due to undifferentiated pleomorphic sarcoma

Pulmonary artery sarcomas are uncommon intracardiac tumours with poor prognosis. We report the case of a 69-year-old woman in good health presenting with rapidly progressive dyspnoea and an unfamiliar systolic murmur. Echocardiography revealed pulmonary valve stenosis due to an obstructing mobile mass. Imaging studies confirmed the presence of a contrast-enhancing lesion adherent to the valve, extending into the pulmonary trunk and right ventricular outflow tract, and suggestive of malignancy. Endovascular biopsy was attempted with no success. Surgical resection with autologous graft valve replacement and pulmonary artery reconstruction was performed. Postoperative histological examination confirmed the diagnosis of an undifferentiated pleomorphic sarcoma. Pulmonary artery sarcoma should be considered as a rare differential diagnosis in patients presenting with dyspnoea and a crescendo-decrescendo systolic murmur increasing with inspiration. Echocardiography is a useful first diagnostic approach but multi-imaging assessment is almost always necessary for definite diagnosis. Our case provides insights into the challenges met by cardiologists, radiologists and cardiac surgeons in the management of such cases

Valley spin polarization by using the extraordinary Rashba effect on silicon

The addition of the valley degree of freedom to a two-dimensional spin-polarized electronic system provides the opportunity to multiply the functionality of next-generation devices. So far, however, such devices have not been realized due to the difficulty to polarize the valleys, which is an indispensable step to activate this degree of freedom. Here we show the formation of 100% spin-polarized valleys by a simple and easy way using the Rashba effect on a system with C-3 symmetry. This polarization, which is much higher than those in ordinary Rashba systems, results in the valleys acting as filters that can suppress the backscattering of spin-charge. The present system is formed on a silicon substrate, and therefore opens a new avenue towards the realization of silicon spintronic devices with high efficiency.X114334Nsciescopu

Formulation of resveratrol into PGA-co-PDL nanoparticles increases its cytotoxic potency against lung cancer cells

Lung cancer is the commonest cause of cancer-related deaths, and current treatment involves the use of cytotoxic drugs which have many unwanted side-effects. Resveratrol, a natural polyphenol, has promising anticancer efficacy, but its therapeutic application is hindered by low bioavailability, which this study sought to improve through encapsulation into nanoparticles (NPs).Resveratrol was loaded into poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL; MWt 16.5 KDa) NPs with sizes between 220-230 nm, and tested against Calu-3 human lung cancer cells. Key findings 5% and 10% resveratrol nanoparticles (RNPs) had a high encapsulation efficiency of 78 ± 0.24% and 70 ± 0.89% and a drug loading of 39 ± 0.12 µg and 70 ± 0.89 µg (w/w), respectively. The PGA-co-PDL blank NP (BNP) at 1 mg/mL had good cytocompatibility when Calu-3 cells were exposed to it for 24 h (cell viability of 87.5±4.7%). Remarkably, the 5% RNP and 10% RNP lowered, up to 80%, the IC50 for 24 h cytotoxicity of resveratrol against the cells, from 158 ± 16 µM to 32 ± 10 µM and 70 ± 13 µM, respectively. Conclusions Loading of resveratrol into PGA-co-PDL NPs increases its anticancer potency, thus enhancing its prospect for treating lung cancer

Delivery of natural phenolic compounds for the potential treatment of lung cancer.

The application of natural products to treat various diseases, such as cancer, has been an important area of research for many years. Several phytochemicals have demonstrated anticarcinogenic activity to prevent or reduce the progression of cancer by modulating various cellular mechanisms. However, poor bioavailability has hindered clinical success and the incorporation of these drugs into efficient drug delivery systems would be beneficial. For lung cancer, local delivery via the pulmonary route would also be more effective. In this article, recent in vitro scientific literature on phenolic compounds with anticancer activity towards lung cancer cell lines is reviewed and nanoparticulate delivery is mentioned as a possible solution to the problem of bioavailability. The first part of the review will explore the different classes of natural phenolic compounds and discuss recent reports on their activity on lung cancer cells. Then, the problem of the poor bioavailability of phenolic compounds will be explored, followed by a summary of recent advances in improving the efficacy of these phenolic compounds using nanoparticulate drug delivery systems. Graphical abstract The rationale for direct delivery of phenolic compounds loaded in microparticles to the lungs

Incidence and Risk Factors of Serious Adverse Events during Antituberculous Treatment in Rwanda: A Prospective Cohort Study

BACKGROUND: Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa. In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome. METHODS AND FINDINGS: Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009. Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28-40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm(3) (IQR 44-248 cells/mm(3)). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23). HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4-8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1-3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1-3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0-2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3-3.0). CONCLUSION: Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections

Sebaceous adenitis in Swedish dogs, a retrospective study of 104 cases

<p>Abstract</p> <p>Background</p> <p>Sebaceous adenitis (SA) is an uncommon, immune mediated skin disease in dogs. The aim was to retrospectively investigate SA in dogs in Sweden with respect to breed, sex and age distribution. A second aim was to retrospectively compare clinical signs in dogs with generalized SA and to estimate the survival after diagnosis in the English springer spaniel, standard poodle and the akita.</p> <p>Methods</p> <p>In total 34 Swedish veterinarians contributed with 104 clinically and histologically verified SA cases. Breed, gender and age at diagnosis were registered for each case. The degree of clinical signs at time for diagnosis and at follow-up and information about treatments, concurrent diseases and euthanasia were recorded for the springer spaniels, standard poodles and akitas using a standardized questionnaire.</p> <p>Results</p> <p>A total of 104 cases of SA were included; most cases were recorded for the springer spaniel (n = 25), standard poodle (n = 21) and the akita (n = 10). These three breeds, together with the lhasa apso and the chow-chow, were the most common when national registry data from the Swedish Board of Agriculture and Swedish Kennel Club were considered. The mean age at diagnosis was 4.8 years. The proportion of males was 61%. When the springer spaniels, standard poodles and the akitas with generalized signs were compared (n = 51), the spaniels showed significantly more severe clinical signs than the poodles at diagnosis regarding alopecia, seborrhoea, pyoderma and the overall severity of clinical signs. At follow-up, the degree of clinical signs for otitis externa and pyoderma differed significantly between the breeds. The estimated median survival time was 42 months.</p> <p>In dogs where data regarding survival was available at the end of the study (n = 44), SA was reported to be the reason for euthanasia in 14 dogs, whereof 7 within 24 months after diagnosis.</p> <p>Conclusion</p> <p>The result of this study implicates that the English springer spaniel is a breed predisposed to SA and that it has more severe clinical signs than the standard poodle. A large proportion of the dogs (spaniel, poodle and akita) investigated regarding survival were reported to have been euthanized to great extent due to the disease.</p

Toward a Unified Genetic Map of Higher Plants, Transcending the Monocot-Dicot Divergence

Closely related (confamilial) genera often retain large chromosomal tracts in which gene order is colinear, punctuated by structural mutations such as inversions and translocations 1. To explore the possibility that conservation of gene order might extrapolate to more distantly related taxa, we first estimated an average structural mutation rate. Nine pairs of taxa, for which there exist both comparative genetic maps and plausible estimates of divergence time, showed an average of0.14 (±0.06) structural mutations per chromosome per million years of divergence (Myr; Table 1). This value is offered as a first approximation, acknowledging that refined comparative data and/or divergence estimates may impel revision