Delay of phagosome maturation by a mycobacterial lipid is reversed by nitric oxide.

Mycobacterium tuberculosis is a facultative intracellular pathogen that inhibits phagosome maturation in macrophages thereby securing survival and growth. Mycobacteria reside in an early endocytic compartment of near-neutral pH where they upregulate production of complex glycolipids such as trehalose dimycolate. Here, we report that trehalose dimycolate coated onto beads increased the bead retention in early phagosomes, i.e. at a similar stage as viable mycobacteria. Thus, a single mycobacterial lipid sufficed to divert phagosome maturation and likely contributes to mycobacterial survival in macrophages. Previous studies showed that activated macrophages promote maturation of mycobacterial phagosomes and eliminate mycobacteria through bactericidal effectors including nitric oxide generated by inducible nitric-oxide synthase. We show that deceleration of bead phagosome maturation by trehalose dimycolate was abolished in immune-activated wild type, but not in activated nitric-oxide synthase-deficient macrophages, nor when hydroxyl groups of trehalose dimycolate were chemically modified by reactive nitrogen intermediates. Thus, specific host defence effectors of activated macrophages directly target a specific virulence function of mycobacteria

Sub-terahertz, microwaves and high energy emissions during the December 6, 2006 flare, at 18:40 UT

The presence of a solar burst spectral component with flux density increasing with frequency in the sub-terahertz range, spectrally separated from the well-known microwave spectral component, bring new possibilities to explore the flaring physical processes, both observational and theoretical. The solar event of 6 December 2006, starting at about 18:30 UT, exhibited a particularly well-defined double spectral structure, with the sub-THz spectral component detected at 212 and 405 GHz by SST and microwaves (1-18 GHz) observed by the Owens Valley Solar Array (OVSA). Emissions obtained by instruments in satellites are discussed with emphasis to ultra-violet (UV) obtained by the Transition Region And Coronal Explorer (TRACE), soft X-rays from the Geostationary Operational Environmental Satellites (GOES) and X- and gamma-rays from the Ramaty High Energy Solar Spectroscopic Imager (RHESSI). The sub-THz impulsive component had its closer temporal counterpart only in the higher energy X- and gamma-rays ranges. The spatial positions of the centers of emission at 212 GHz for the first flux enhancement were clearly displaced by more than one arc-minute from positions at the following phases. The observed sub-THz fluxes and burst source plasma parameters were found difficult to be reconciled to a purely thermal emission component. We discuss possible mechanisms to explain the double spectral components at microwaves and in the THz ranges.Comment: Accepted version for publication in Solar Physic

Phenotype of p53 wild-type epitope-specific T cells in the circulation of patients with head and neck cancer

CD8(+) cytotoxic T-cell (CTL) specific for non-mutated, wild type (wt) sequence p53 peptides derived from wt or mutant p53 molecules expressed in head and neck squamous cell carcinomas (HNSCC) have been detected in the circulation of patients with this disease. The frequency and differentiation/maturation phenotypes of these anti-tumor specific CTL can reflect the host's immunologic response. Therefore, we investigated the frequency and phenotypes of wt sequence p53 peptide-specific CTL in patients with HNSCC (n = 33) by flow cytometric analysis using HLA-A*0201 tetrameric peptides (tet) complexed with the wt sequence p53(264-272) or p53(149-157) peptide and co-staining with phenotypic markers. One main finding was that increasing frequencies of tet(+) CD8(+) T cells in patients' circulation correlated with increased frequencies of inactive naive tet(+) cells, while those with effector memory and terminally differentiated phenotypes, which are associated with positive anti-tumor immune responses, decreased. We also found that the frequency of circulating tet(+) CD8(+) T cells negatively correlated with p53 expression in tumor tissues and tumor stage. Our findings support further clinical-based investigations to define the frequencies and phenotypes of wt sequence p53 peptide-specific CD8(+) T cells to predict disease severity, enhance selection of patients for inclusion in vaccination trials and highlight prerequisites to enhance immune susceptibility by activation of inactive naive tet+ T cells and/or enhancing circulating effector T cell activity by checkpoint blockage

UTILITY OF FIBEROPTIC BRONCHOSCOPY FOR RETRIEVAL OF ASPIRATED HEADSCARF PINS

Background: Tracheobronchial foreign body aspiration is a worldwide health problem which often results in life threatening complications.Headscarf pin aspiration is a common and unique form of foreign body aspiration among young Muslim women. Rigid bronchoscopy (RB) is considered the standard procedure for retrieval. Standard flexible bronchoscopy (FOB) is used increasingly in the treatment of tracheobronchial headscarf pins aspiration in adults.Aim: The aim of this study is to evaluate the utility (use) of FOB for the retrieval (extraction) of aspirated headscarf pins.Materials and Methods: Patients with the diagnosis of headscarf pin aspiration admitted to Sulaimanyah Teaching Hospital, department of cardiothoracic and vascular Surgery from January 2008 to September 2011 were included in the study. Standard FOB procedure using an oral approach with patient in recumbent position, under local anesthesia and conscious sedation was performed as the primary tool for retrieval.Results: A total of 20 cases were admitted during the study period. The mean age of the sample was 24 years (10-40 years).All patients presented with cough while two of them had hemoptysis (10%) and five had unilateral wheeze on chest auscultation (25%). The aspirated pin was successfully retrieved in 19/20 cases (95%) during the first attempt of FOB. However, FOB was not successful in 1/20 case (5%). The aspirated pin was successfully retrieved by RB under general anesthesia.Conclusions: FOB is a safe and successful method when performed by an experienced bronchoscopist, well educated staff, and at a well equipped bronchoscopy unit. Headscarf pin aspiration is a relatively common form of foreign body aspiration among young Muslim Iraqi women. It commonly occurs when women hold the pins in their teeth while wearing the hejaab and talking to others at the same time

Content Disputes in Wikipedia Reflect Geopolitical Instability

Indicators that rank countries according socioeconomic measurements are important tools for regional development and political reform. Those currently in widespread use are sometimes criticized for a lack of reproducibility or the inability to compare values over time, necessitating simple, fast and systematic measures. Here, we applied the ‘guilt by association’ principle often used in biological networks to the information network within the online encyclopedia Wikipedia to create an indicator quantifying the degree to which pages linked to a country are disputed by contributors. The indicator correlates with metrics of governance, political or economic stability about as well as they correlate with each other, and though faster and simpler, it is remarkably stable over time despite constant changes in the underlying disputes. For some countries, changes over a four year period appear to correlate with world events related to conflicts or economic problems

A worrying arrival: the first record of brown macroalga Rugulopteryx okamurae in Madeira Island and its invasive risk

The brown macroalgae Rugulopteryx okamurae is described as one of the most severe and threatening invasive marine macroalgae in European waters. This study reports the first record of R. okamurae in the Madeira archipelago, which represents a new southern distribution limit of this species in NE Atlantic European waters. Morphological and molecular characters were used to confirm the species' identity, and its potential invasion risk in Madeiran waters was screened using the standard risk assessment tool AS-ISK. Results show that R. okamurae has a medium-high risk of becoming invasive in Madeira Island under present and future climate scenarios. The greater risk of impact involves suppressing local species growth and the modification and degradation of local habitats, including trophic cascade effects. However, environmental and commercial impacts could also occur in case of an explosion of the invasive populations. This new introduction in Madeira coastal waters emphasises the need for regular monitoring of R. okamurae, particularly to assess population dynamics to avoid establishing and further expansions. Finally, we recommend the evaluation of the possible derived impacts affecting rocky coastal communities and adopting the necessary mitigation measures and policies

Influence of smoking on the prognostic value of cardiovascular computed tomography coronary angiography

Aims Computed tomography coronary angiography (CTA) is an important non-invasive imaging modality increasingly used for the diagnosis and prognosis of coronary artery disease (CAD). The purpose of the current study was to determine the influence of smoking status on the prognostic value of CTA in patients with suspected or known CAD. Methods and results In 1207 patients (57% male, age 57 ± 12 years) referred for CTA, the presence of significant CAD (≥50% stenosis) was determined. During follow-up (FU) the following events were recorded: all cause mortality, and non-fatal infarction. The prognostic value of CTA in smokers and non-smokers was compared using an interaction term in the Cox proportional hazard regression analysis. Significant CAD was observed in 327 patients (27%), and 273 patients (23%) were smokers. During a median FU time of 2.2 years, an event occurred in 50 patients. After correction for baseline characteristics including smoking in a multivariate model, significant CAD remained an independent predictor of events. Furthermore, a significant interaction (P < 0.05) was observed between significant CAD and smoking. The annualized event rate in smokers with significant CAD was 8.78% compared with 0.99% in smokers without significant CAD (P < 0.001). In non-smokers with significant CAD the annualized event rate was 2.07% compared with 1.01% in non-smokers without significant CAD (P= 0.058). Conclusion The prognostic value of CTA was significantly influenced by smoking status. The event rates in patients with significant CAD were approximately four-fold higher in smokers compared with non-smokers. These findings suggest that smoking cessation needs to be aggressively pursued, especially in smokers with significant CA

European Expert Opinion on ANT-DBS therapy for patients with drug-resistant epilepsy (a Delphi consensus)

Introduction: Although deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) represents an established third-line therapy for patients with drug-resistant focal epilepsy, guiding reports on practical treatment principles remain scarce. Methods: An Expert Panel (EP) of 10 European neurologists and 4 neurosurgeons was assembled to share their experience with ANT-DBS therapy. The process included a review of the current literature, which served as a basis for an online survey completed by the EP prior to and following a face-to-face meeting (Delphi method). An agreement level of >= 71 % was considered as consensus. Results: Out of 86 reviewed studies, 46 (53 %) were selected to extract information on the most reported criteria for patient selection, management, and outcome. The Delphi process yielded EP consensus on 4 parameters for selection of good candidates and patient management as well as 7 reasons of concern for this therapy. Since it was not possible to give strict device programming advice due to low levels of evidence, the experts shared their clinical practice: all of them start with monopolar stimulation, 79 % using the cycling mode. Most (93 %) EP members set the initial stimulation frequency and pulse width according to the SANTE parameters, while there is more variability in the amplitudes used. Further agreement was achieved on a list of 7 patient outcome parameters to be monitored during the follow-up. Conclusions: Although current evidence is too low for definite practical guidelines, this EP report could support the selection and management of patients with ANT-DBS

Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue

Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD