The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Stone clearance in lower pole nephrolithiasis after extra corporeal shock wave lithotripsy – the controversy continues

BACKGROUND: To determine factors influencing the clearance of fragments after extra-corporeal shock wave lithotripsy (ESWL) for lower pole calyceal (LPC) stones. METHODS: In the period between July 1998 and Oct 2001, 100 patients with isolated lower polar calyceal calculi ≤ 20 mm, in patients aged ≥ 14 years, were included in the study. Intravenous urograms (IVU) were reviewed to define the LPC anatomy (width of the infundibulum and pelvicalyceal angle). Study end points i.e. stone free status; number of shock waves used and number of sessions were correlated with variables like LPC anatomy, body mass index and stone size. RESULTS: At three months follow up the clearance for stone size ≤ 10 mm, 11–15 mm and 16–20 mm were 95, 96 and 90% respectively. Patients with acute LPC (<90°) and obtuse angle (>90°) had stone clearance of 94 and 100% respectively. For the infundibular width of < 4 mm, the stone clearance was 93% were as for > 4 mm, it was 100%. For body mass index (BMI) less than and > 30 kg/m(2), the stone clearance was 92 and 95% respectively. CONCLUSIONS: There is a trend towards more ESWL sessions and shock wave requirement in patients with acute pelvi-calyceal angle and narrow infundibulum but it is not statistically significant. Size (≤ 20 mm) and BMI has no relation with stone clearance. With modern lithotripter, stones up to 20 mm could primarily be treated by ESWL, irrespective of an un-favorable lower polar calyceal anatomy and body habitus

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum