Prior Bordetella pertussis infection modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma

Background It has been proposed that T helper (Th)2-driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter-regulation can protect against allergic asthma. Objective To test whether Th1-inducing infection with Bordetella pertussis protects against allergic asthma using well-characterized murine models. Methods Groups of mice were sensitized to ovalbumin (OVA) in the presence or absence of B. pertussis, a well-characterized Th1 inducing respiratory infection. Immunological, pathological and physiological parameters were measured to assess the impact of infection on immune deviation and airway function. Results We demonstrate that OVA sensitization does not affect the development of B. pertussisspecific immune responses dominated by IgG2a and IFN-g and does not impair Th1-mediated clearance of airway infection. In contrast, B. pertussis infection at the time of sensitization modulated the response to OVA and significantly reduced total serum and OVA-specific IgE. The pattern of cytokine responses, in particular OVA-specific IL-5 responses in the spleen was also modulated. However, B. pertussis did not cause global suppression as IL-10 and IL-13 levels were enhanced in OVA-stimulated spleen cell cultures and in lavage fluid from infected co-sensitized mice. Histopathological examination revealed that B. pertussis infection prior to OVA sensitization resulted in increased inflammation of bronchiolar walls with accompanying hyperplasia and mucous metaplasia of lining epithelia. These pathological changes were accompanied by increased bronchial hyper-reactivity to methacholine exposure. Conclusion Contrary to the above premise, a Th1 response induced by a common childhood infection does not protect against bronchial hyper-reactivity, but rather exacerbates the allergic asthmatic response, despite modulation of immune mediators

gamma-delta T Cells Regulate the Early Inflammatory Response to Bordetella pertussis Infection in the Murine Respiratory Tract

The role of T cells in the regulation of pulmonary inflammation following Bordetella pertussis infection was investigated. Using a well-characterized murine aerosol challenge model, inflammatory events in mice with targeted disruption of the T-cell receptor -chain gene (TCR mice) were compared with those in wild-type animals. Early following challenge with B. pertussis, TCR mice exhibited greater pulmonary inflammation, as measured by intra-alveolar albumin leakage and lesion histomorphometry, yet had lower contemporaneous bacterial lung loads. The larger numbers of neutrophils and macrophages and the greater concentration of the neutrophil marker myeloperoxidase in bronchoalveolar lavage fluid from TCR mice at this time suggested that differences in lung injury were mediated through increased leukocyte trafficking into infected alveoli. Furthermore, flow cytometric analysis found the pattern of recruitment of natural killer (NK) and NK receptor T cells into airspaces differed between the two mouse types over the same time period. Taken together, these findings suggest a regulatory influence for T cells over the early pulmonary inflammatory response to bacterial infection. The absence of T cells also influenced the subsequent adaptive immune response to specific bacterial components, as evidenced by a shift from a Th1 to a Th2 type response against the B. pertussis virulence factor filamentous hemagglutinin in TCR mice. The findings are relevant to the study of conditions such as neonatal B. pertussis infection and acute respiratory distress syndrome where T cell dysfunction has been implicated in the inflammatory process

From black strings to black holes: nuttier and squashed AdS5_5 solutions

We construct new solutions of the Einstein equations with negative cosmological constant in five spacetime dimensions. They smoothly emerge as deformations of the known AdS$_5$ black strings. The first type of configurations can be viewed as the $d=4$ Taub-NUT-AdS solutions uplifted to five dimensions, in the presence of a negative cosmological constant. We argue that these solutions provide the gravity dual for a ${\cal N}=4$ super-Yang-Mills theory formulated in a $d=4$ homogeneous G\"odel-type spacetime background. A different deformation of the AdS$_5$ black strings leads to squashed AdS black holes and their topological generalizations. In this case, the conformal infinity is the product of time and a circle-fibration over a base space that is a two-dimensional Einstein space.Comment: 19 pages, 7 figure

Coaches' learning and sustainability in high performance sport

In undertaking their complicated and multi-faceted work, high performance coaches have previously been shown to be influential in the performance of athletes. It has also been noted that high performance coaches are learners by necessity. However, what remains unclear is how coaches' learning influences their engagement in sustainable practice. This study draws on three cohorts of full-time high performance coaches employed in Olympic and professional sports throughout Australia. Semi-structured interviews were conducted face-to-face and were inductively analysed. The results revealed that the coaches were presented with a variety of opportunities to learn, with the most valued sources being 'learning on the job', 'discussions with others' and 'experience as athletes'. These unmediated learning opportunities are critiqued along with other mediated opportunities in relation to notions of sustainability. The dominance of unmediated sources of learning meant that sustainable practice was present but was not assured. Sustainable practice is also discussed in relation to the dominant models of high performance athlete development and the demands of coaching work

Two Types of Planning in Neighborhoods

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68338/2/10.1177_0739456X8400300209.pd

Observation of Events with an Energetic Forward Neutron in Deep Inelastic Scattering at HERA

In deep inelastic neutral current scattering of positrons and protons at the center of mass energy of 300 GeV, we observe, with the ZEUS detector, events with a high energy neutron produced at very small scattering angles with respect to the proton direction. The events constitute a fixed fraction of the deep inelastic, neutral current event sample independent of Bjorken x and Q2 in the range 3 · 10-4 \u3c xBJ \u3c 6 · 10-3 and 10 \u3c Q2 \u3c 100 GeV2

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362