Electrically charged compact stars

We review here the classical argument used to justify the electrical neutrality of stars and show that if the pressure and density of the matter and gravitational field inside the star are large, then a charge and a strong electric field can be present. For a neutron star with high pressure (~ 10^{33} to 10^{35} dynes /cm^2) and strong gravitational field (~ 10^{14} cm/s^2), these conditions are satisfied. The hydrostatic equation which arises from general relativity, is modified considerably to meet the requirements of the inclusion of the charge. In order to see any appreciable effect on the phenomenology of the neutron stars, the charge and the electrical fields have to be huge (~ 10^{21} Volts/cm). These stars are not however stable from the viewpoint that each charged particle is unbound to the uncharged particles, and thus the system collapses one step further to a charged black holeComment: Proceedings of 10th Marcel Grossmann Meeting on Recent Developments in Theoretical and Experimental General Relativity, Gravitation and Relativistic Field Theories (MG X MMIII), Rio de Janeiro, Brazil, 20-26 Jul 200

Influence of thresholding in mass and entropy dimension of 3-D soil images

With the advent of modern non-destructive tomography techniques, there have been many attempts to analyze 3-D pore space features mainly concentrating on soil structure. This analysis opens a challenging opportunity to develop techniques for quantifying and describe pore space properties, one of them being fractal analysis. Undisturbed soil samples were collected from four horizons of Brazilian soil and 3-D images at 45μm resolution. Four different threshold criteria were used to transform computed tomography (CT) grey-scale imagery into binary imagery (pore/solid) to estimate their mass fractal dimension (Dm) and entropy dimension (D1). Each threshold criteria had a direct influence on the porosity obtained, varying from 8 to 24% in one of the samples, and on the fractal dimensions. Linear scaling was observed over all the cube sizes, however depending on the range of cube sizes used in the analysis, Dm could vary from 3.00 to 2.20, realizing that the threshold influenced mainly the scaling in the smallest cubes (length of size from 1 to 16 voxels). Dm and D1 showed a logarithmic relation with the apparent porosity in the image, however, the increase of both values respect to porosity defined a characteristic feature for each horizon that can be related to soil texture and depth

Respiratory infections: a global burden

Respiratory infections are accountable for significant morbidity, and mortality world-wide. Amongst all diseases, lower respiratory tract infections have the greatest burden on human health, with a two and six-fold greater disability-adjusted life years compared to ischaemic heart disease and diabetes mellitus, respectively. Not only do pathogens cause primary respiratory infection such as pneumonia, but they also play a paramount role in the exacerbations of chronic lung diseases such as chronic obstructive pulmonary disease, interstitial lung disease and bronchiectasis. Lower respiratory tract infections, excluding tuberculosis, are the third biggest global killers, responsible for 3.2 million deaths in 2015. Importantly, in low-income countries lower respiratory tract infections remain the top cause of death. This is linked to poverty, which is associated with malnutrition, overcrowding, and air pollution, which increases the risk of infection with airborne pathogens. The majority of these infections are avoidable, but due to a lack of resources and access to healthcare people do not have access to immunisations or get timely antibiotics. In this setting, the enormous burden of human immunodeficiency virus (HIV) infection augments the risk of infections with common, as well as, opportunistic respiratory pathogens. In contrast, in high-income countries, there is better access to immunisations and medications, but an ageing population, increased prevalence of chronic lung disease and iatrogenic immunosuppression are driving the incidence of respiratory infections. It is estimated that by 2050, 2 billion of the world’s population will be older than 65 years and >1 billion people will have a preventable chronic lung disease and unless respiratory infections can be prevented in these at-risk groups, healthcare systems will not cope with the disease burden. Furthermore, modern treatments for chronic inflammatory/autoimmune disease and cancer with drugs that impact on immunity to pathogens has led to the appreciation of the increased risk of acquiring respiratory infections amongst these individuals. Importantly, we are living in an era where antibiotics that previously were efficacious are no longer effective due to the increasing presence of drug-resistance pathogens, and new antibiotics are taking too long to come through the pipe-line. Even in the presence of effective anti-microbial therapy multi-morbidity and mortality is still unavoidable for many patients with severe infections due to the exaggerated host response and bystander tissue injury. Therefore, although there is more control over the spread of communicable diseases and improvements in supportive care for critically ill patients, the impact of respiratory pathogens on human health remains so great that we must not stop our journey to better understand host-pathogen interactions and identify novel preventative and therapeutic strategies

Regulation of neutrophilic inflammation by proteinase-activated receptor 1 during bacterial pulmonary infection

Neutrophils are key effector cells of the innate immune response to pathogenic bacteria, but excessive neutrophilic inflammation can be associated with bystander tissue damage. The mechanisms responsible for neutrophil recruitment to the lungs during bacterial pneumonia are poorly defined. In this study, we focus on the potential role of the major high-affinity thrombin receptor, proteinase-activated receptor 1 (PAR-1), during the development of pneumonia to the common lung pathogen Streptococcus pneumoniae. Our studies demonstrate that neutrophils were indispensable for controlling S. pneumoniae outgrowth but contributed to alveolar barrier disruption. We further report that intra-alveolar coagulation (bronchoalveolar lavage fluid thrombin-antithrombin complex levels) and PAR-1 immunostaining were increased in this model of bacterial lung infection. Functional studies using the most clinically advanced PAR-1 antagonist, SCH530348, revealed a key contribution for PAR-1 signaling in influencing neutrophil recruitment to lung airspaces in response to both an invasive and noninvasive strain of S. pneumoniae (D39 and EF3030) but that PAR-1 antagonism did not impair the ability of the host to control bacterial outgrowth. PAR-1 antagonist treatment significantly decreased pulmonary levels of IL-1β, CXCL1, CCL2, and CCL7 and attenuated alveolar leak. Ab neutralization studies further demonstrated a nonredundant role for IL-1β, CXCL1, and CCL7 in mediating neutrophil recruitment in response to S. pneumoniae infection. Taken together, these data demonstrate a key role for PAR-1 during S. pneumoniae lung infection that is mediated, at least in part, by influencing multiple downstream inflammatory mediators

Adult pneumococcal vaccination: advances, impact, and unmet needs

PURPOSE OF REVIEW: Preventing pneumonia in the elderly and study participants individuals with comorbidities is an unmet clinical need. Streptococcus pneumoniae is the commonest bacterial cause of pneumonia, and we summarize recent findings regarding current S. pneumoniae vaccines, and debate their efficacy and cost-effectiveness in risk groups. We also discuss potential future vaccine strategies such as protein antigen vaccines. RECENT FINDINGS: Current vaccination with pneumococcal polysaccharide vaccine does not prevent S. pneumoniae pneumonia. Vaccination with pneumococcal conjugated vaccine (PCV) prevents nasopharyngeal colonization, but although PCV13 has recently been shown to prevent S. pneumoniae pneumonia in adults, its overall efficacy was relatively low. The results of cost-effectiveness studies of PCV vaccination in adults are variable with some showing this is a cost-effective strategy, whereas others have not. The lack of cost-effectiveness is predominantly because of the current cost of the PCV vaccine and the existing herd immunity effect from childhood PCV vaccination on vaccine serotypes. SUMMARY: S. pneumoniae pneumonia is a vaccine-preventable disease but remains a common cause of morbidity and mortality. Advances in vaccination using approaches that induce serotypes-independent immunity and are immunogenic in high-risk groups are required to reduce the burden of disease because of S. pneumoniae

Opportunistic bacterial, viral and fungal infections of the lung

Opportunistic infections are a major cause of morbidity and mortality in severely immunocompromised patients, such as those receiving chemotherapy or biological therapies, patients with haematological malignancy, aplastic anaemia or HIV infection, and recipients of solid-organ or stem cell transplants. The type and degree of the immune defect dictate the profile of potential opportunistic pathogens; T-cell-mediated defects increase the risk of viral (cytomegalovirus, respiratory viruses) and Pneumocystis jirovecii infections, whereas neutrophil defects are associated with bacterial pneumonia and invasive aspergillosis. However, patients often have combinations of immune defects, and a wide range of other opportunistic infections can cause pneumonia. Importantly, conventional non-opportunistic pathogens are frequently encountered in immunocompromised hosts and should not be overlooked. The radiological pattern of disease (best assessed by computed tomography) and speed of onset help to identify the likely pathogen(s); radiological imaging can subsequently be supported by targeted investigation including the early use of bronchoscopy in selected patients. Rapid and expert clinical assessment can identify the most likely pathogens, which can then be treated aggressively, providing the best opportunity for a positive clinical outcome

Predicting bacteraemia or rapid identification of the causative pathogen in community acquired pneumonia: where should the priority lie?

Improved microbiological (molecular) diagnostic tests are needed to rapidly identify causative pathogens in CAP http://ow.ly/6H0X300KBe

ICAM-1 and ICAM-2 Are Differentially Expressed and Up-Regulated on Inflamed Pulmonary Epithelium, but Neither ICAM-2 nor LFA-1: ICAM-1 Are Required for Neutrophil Migration Into the Airways In Vivo

Neutrophil migration into the airways is an important process to fight infection and is mediated by cell adhesion molecules. The intercellular adhesion molecules, ICAM-1 (CD54) and ICAM-2 (CD102) are known ligands for the neutrophil integrins, lymphocyte function associated antigen (LFA)-1 (αLβ2; CD11a/CD18), and macrophage-1 antigen (Mac-1;αMβ2;CD11b/CD18) and are implicated in leukocyte migration into the lung. However, it is ill-defined how neutrophils exit the lung and the role for ICAMs in trans-epithelial migration (TEpM) across the bronchial or alveolar epithelium. We found that human and murine alveolar epithelium expressed ICAM-1, whilst the bronchial epithelium expressed ICAM-2, and both were up-regulated during inflammatory stimulation in vitro and in inflammatory lung diseases such as cystic fibrosis. Although β2 integrins interacting with ICAM-1 and -2 mediated neutrophil migration across human bronchial epithelium in vitro, neither ICAM-2 nor LFA-1 binding of ICAM-1 mediated murine neutrophil migration into the lung or broncho-alveolar space during LPS-induced inflammation in vivo. Furthermore, TEpM of neutrophils themselves resulted in increased epithelial junctional permeability and reduced barrier function in vitro. This suggests that although β2 integrins interacting with ICAMs may regulate low levels of neutrophil traffic in healthy lung or early in inflammation when the epithelial barrier is intact; these interactions may be redundant later in inflammation when epithelial junctions are disrupted and no longer limit TEpM

Evidence for chemokine synergy during neutrophil migration in ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. OBJECTIVES: The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. METHODS: CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. RESULTS: CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. CONCLUSION: This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS