Stratifying a Risk for an Increased Variation of Airway Caliber among the Clinically Stable Asthma

ABSTRACTBackgroundRecently, correlations of peak expiratory flow (PEF) variation have been shown to facilitate the prediction of later asthma symptoms and exacerbations. However, it has not been fully examined whether or not any patient characteristics are associated with the residual airway lability in treated asthmatics. The objective of this study is to examine a predictive marker for increased variation of PEF in patients with clinically stable asthma.MethodsWe studied 297 asthmatic patients who were monitored for PEF twice a day. Asthma Control Questionnaire (ACQ), spirometry, and exhaled nitric oxide fraction (FENO) were measured. After the assessment of baseline values, PEF measuring was continued and associations between these clinical markers and later variation of PEF over a week (Min%Max) were investigated.Results17.5% of the subjects showed increased PEF variability (Min%Max < 80%). ACQ, forced expiratory volume in 1 s % of predicted (%FEV1), and FENO were identified as independent predictors of Min%Max < 80%. An ACQ ≥ 0.4 yielded 96% sensitivity and 59% specificity, a %FEV1 ≤ 85% yielded 62% sensitivity and 89% specificity, and a FENO ≥ 40 ppb yielded 75% sensitivity and 90% specificity for identifying the subjects with high variability in PEF. When we combine %FEV1 ≤ 85% and FENO ≥ 40 ppb, this index showed the highest specificity (98%) for increased PEF variability.ConclusionsThese results indicate that ACQ, %FEV1 and FENO can stratify the risk for increased variation in airway caliber among patients with stable asthma. This may help identify subjects in whom further monitoring of lung function fluctuations is indicated

Dynamics of light-induced anomalous Hall effect in the three-dimensional Dirac semimetal Cd3_3As2_2

We experimentally study the dynamical behavior of the light-induced anomalous Hall effect in a three-dimensional Dirac semimetal, Cd$_3$As$_2$. An ultrashort, circularly polarized, multi-terahertz pump pulse breaks the time-reversal symmetry of a thin film sample. The resulting anomalous Hall effect is clearly observed through the polarization rotation of a single-cycle terahertz probe pulse. Comparing the experimental result with theory, we find that the field-induced injection current dominates the anomalous Hall effect during pump irradiation, while the Berry curvature of the Floquet-Weyl semimetal state does not appreciably contribute. Remarkably, even after pump irradiation, we observe an anomalous Hall effect that lasts for more than 10 ps. A model fit to the Hall conductivity spectrum reveals a relatively long scattering time over 400 fs. This result shows that circularly polarized light creates a polarization of the isospin degree of freedom in the Dirac semimetal, which labels the crystallographic point group representation of the overlapping Weyl semimetal bands. Our observation paves the way for conversion of a robust isospin flow into an electric current at room temperature, being a new analogue of the inverse spin Hall effect.Comment: 44 pages, 14 figure

Immunotherapy of transitional cell carcinoma of urinary bladder

Karcinom prijelaznog epitela mokraćnog mjehura najčešći je karcinom mokraćnog sustava. Klinički razlikujemo dva oblika ove bolesti: mišićno-neinvazivni i mišićno-invazivni oblik. Temeljna klinička odrednica mišićno-neinvazivnih tumora su recidivne novotvorinske promjene; 60 – 90 % mišićno-neinvazivnih tumora recidivirat će ako se liječe samo transuretralnom resekcijom (TUR). Upravo stoga se nakon TUR-a u pacijenata u kojih postoji visoki rizik od ponovne pojave ili progresije bolesti provodi intravezikalna imunoterapija BCGom (bacillus Calmette-Guerin). BCG predstavlja živi atenuirani soj Mycobacterium bovis. U primjeni BCG-a intravezikalne terapije razlikujemo indukcijsku terapiju i terapiju održavanja. Intravezikalna aplikacija BCG-a uzrokuje masivan ulazak upalnih stanica u stijenku mokraćnog mjehura te produkciju citokina detektibilnih u sluznici mjehura i u urinu, što dovodi do imunog odgovora protiv tumora. Činjenica je kako BCG uzrokuje dugotrajan i dugodjelujući imuni odgovor. Do eradikacije tumorskih stanica dolazi zbog celularnih fokusa u stijenci mjehura, a kao direktan antitumorski efektorski mehanizam navodi se direktna antitumorska aktivnost IFN (interferon) i citotoksičnost NK (engl. natural killer) stanica.Bladder cancer is the most common cancer in urinary system. There are two clinical aspects of this disease: muscle non-invasive and muscle invasive disease. Basic characteristic of non-muscle invasive disease is tumor recurrence; 60-90 % of tumors will recurr if treated by transurethral resection (TUR) only. That is the reason why patients in whom exists the risk of recurrence or progression undergo intravesical bacillus Calmette-Guerin (BCG) immunotherapy. BCG represents live attenuated Mycobacterium bovis. There are two phases in BCG therapy: induction and maintenance therapy. Intravesical BCG application causes massive agregation of immune cells in bladder wall and producton of cytokins which causes cytotoxic tumor response. Direct effector mechanism is achieved by IFN (interferon) and NK (natural killer) cell cytotoxicity

Increased Level of Pericardial Insulin-Like Growth Factor-1 in Patients With Left Ventricular Dysfunction and Advanced Heart Failure

ObjectivesTo test the hypothesis that the cardiac insulin-like growth factor-1 (IGF-1) system is up-regulated in the failing heart, we measured the pericardial (cardiac) and plasma (circulating) IGF-1 levels in coronary artery disease patients.BackgroundLocal IGF-1 systems are regulated differently from the systemic IGF-1 system. The cardiac IGF-1 system is up-regulated by the increased left ventricular (LV) wall stress. However, it remains unknown how this system is affected in LV dysfunction and heart failure.MethodsWe measured the plasma and pericardial fluid levels of IGF-1 and brain natriuretic peptide (BNP) in 87 coronary artery disease patients undergoing cardiac surgery, and examined their relationships with LV function and heart failure severity. The expressions of IGF-1 and IGF-1 receptor proteins were examined in endomyocardial biopsies obtained from other patients with normal or impaired LV function.ResultsThe pericardial IGF-1 and BNP levels were positively correlated with the plasma BNP level (both p < 0.001). The pericardial IGF-1 level was increased in heart failure patients, whereas the plasma IGF-1 level was rather decreased. The pericardial IGF-1 level was inversely correlated with the LV ejection fraction (p < 0.001), whereas the plasma IGF-1 level was not. Positive immunostaining for IGF-1 and IGF-1 receptor proteins was enhanced in myocardial biopsies from failing hearts compared with those from nonfailing hearts.ConclusionsThe pericardial IGF-1 level was increased in patients with LV dysfunction and heart failure, whereas the plasma IGF-1 level was decreased. These results may indicate that up-regulation of the cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction

Increase of nitrosative stress in patients with eosinophilic pneumonia

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP). We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.</p> <p>Methods</p> <p>Exhaled NO including fractional exhaled NO (FE_NO) and Calv was measured in ten healthy subjects, 13 patients with idiopathic pulmonary fibrosis (IPF), and 13 patients with EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment for 4 weeks.</p> <p>Results</p> <p>The Calv levels in the EP group (14.4 ± 2.0 ppb) were significantly higher than those in the healthy subjects (5.1 ± 0.6 ppb, p < 0.01) and the IPF groups (6.3 ± 0.6 ppb, p < 0.01) as well as the FE_NOand the corrected Calv levels (all p < 0.01). More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant positive correlations with both iNOS (r = 0.858, p < 0.05) and 3-NT positive cells (r = 0.924, p < 0.01). Corticosteroid treatment significantly reduced both the FE_NO(p < 0.05) and the Calv levels (p < 0.01). The magnitude of reduction in the Calv levels had a significant positive correlation with the peripheral blood eosinophil counts (r = 0.802, p < 0.05).</p> <p>Conclusions</p> <p>These results suggested that excessive nitrosative stress occurred in EP and that Calv could be a marker of the disease activity.</p