Allergen-specific immunotherapy (ASIT) has the potential to modify allergic diseases, and it is also considered a potential therapy for allergic asthma. House dust mite (HDM) allergens, a common source of airborne allergen in human diseases, have been developed as an immunotherapy for patients with allergic asthma via the subcutaneous and sublingual routes. Oral immunotherapy with repeated allergen ingestion is emerging as another potential modality of ASIT. The aim of this study was to evaluate the therapeutic efficacy of the oral ingestion of HDM extracts in a murine model of allergic asthma.BABL/c mice were sensitized twice by intraperitoneal injection of HDM extracts and Al(OH)3 on day 1 and day 8. Then, the mice received challenge to induce airway inflammation by intratracheal instillation of HDM extracts on days 29-31. The treatment group received immunotherapy with oral HDM extracts ingestion before the challenge. All the mice were sacrificed on day 32 for bronchoalveolar inflammatory cytokines, mediastinal lymph node T cells, lung histology, and serum HDM-specific immunoglobulins analyses.Upon HDM sensitization and following challenge, a robust Th2 cell response and eosinophilic airway inflammation were observed in mice of the positive control group. The mice treated with HDM extracts ingestion had decreased eosinophilic airway inflammation, suppressed HDM-specific Th2 cell responses in the mediastinal lymph nodes, and attenuated serum HDM-specific IgE levels.Oral immunotherapy with HDM extracts ingestion was demonstrated to have a partial therapeutic effect in the murine model of allergic asthma. This study may serve as the basis for the further development of oral immunotherapy with HDM extracts in allergic asthma.
Light efficiency optimization of a direct‐type backlight unit (BLU) of the liquid crystal display (LCD) is considered in this paper. The purpose of this research is to obtain the greatest uniformity in a direct‐type BLU, while the brightness is maintained in a satisfactory level.It is difficult to find a numerical optimization algorithm that is readily applicable to this problem because of the existence of discrete variables, implicit objective functions and constraints, or even binary constraints. The sequential neural‐network approximation (SNA) method is designed specifically for this type of engineering design optimization problem. In this paper, a two variable LCD BLU design example is presented first to illustrate the design process using the SNA method. Then a four variable LCD BLU design optimization problem is solved.
Background The clinical impact of bacterial and mycobacterial isolates on bronchiectasis remains uncertain. Materials and methods Patients with bronchiectasis at 16 hospitals in Taiwan were recruited with a 1-year follow-up. The patients were classified into six groups: Group 1, Pseudomonas aeruginosa ; Group 2, Klebsiella pneumoniae ; Group 3, Other bacteria; Group 4, Non-tuberculous mycobacteria (NTM); Group 5, Daily sputum without bacterial or NTM colonization; and Group 6, Dry bronchiectasis. Results A total of 1416 patients (mean age, 67 years; males, 43%) were included. The mean modified Reiff score was 5 (range: 1–18). Fifty-nine percent (829 patients) had sputum, whereas the remaining did not. The proportions of bacteria and NTM cultured from sputum within one year of observation were 27% (381/1416) and 15% (202/1416), respectively. The most common bacterial isolate was P. aeruginosa (13%), followed by K. pneumoniae (7%). Twenty-six percent of the patients experienced severe exacerbations at least once within the year. The one-year all-cause mortality rate was 3%. Patients with sputum exhibited a higher rate of severe exacerbations compared to that in patients with dry bronchiectasis, regardless of the presence of bacteria or NTM (p<0·001). Patients with bacterial colonization had a higher mortality rate (p<0·001). Further, the highest mortality rate was observed among those with K. pneumoniae colonization (hazard ratio [HR]: 8.39, 95% confidence interval [95% CI]: 2.39–29.49), followed by individuals colonized with other bacteria (HR: 8.04, 95% CI: 2.36–27.38) and P. aeruginosa (HR: 7.83, 95% CI: 2.45–25.03). Additionally, old age was an independent risk factor (HR, 2.72; 95% CI: 1.19–6.18). Conclusion K. pneumoniae was more frequently isolated from patients with bronchiectasis in Taiwan, compared with Western countries and was associated with unfavorable clinical outcomes.
The prognosis of different etiologies of liver cirrhosis (LC) is not well understood. Previous studies performed on alcoholic LC-dominated cohorts have demonstrated a few conflicting results. We aimed to compare the outcome and the effect of comorbidities on survival between alcoholic and non-alcoholic LC in a viral hepatitis-dominated LC cohort. We identified newly diagnosed alcoholic and non-alcoholic LC patients, aged ≥40 years old, between 2006 and 2011, by using the Longitudinal Health Insurance Database. The hazard ratios (HRs) were calculated using the Cox proportional hazards model and the Kaplan–Meier method. A total of 472 alcoholic LC and 4313 non-alcoholic LC patients were identified in our study cohort. We found that alcoholic LC patients were predominantly male (94.7% of alcoholic LC and 62.6% of non-alcoholic LC patients were male) and younger (78.8% of alcoholic LC and 37.4% of non-alcoholic LC patients were less than 60 years old) compared with non-alcoholic LC patients. Non-alcoholic LC patients had a higher rate of concomitant comorbidities than alcoholic LC patients (79.6% vs. 68.6%, p < 0.001). LC patients with chronic kidney disease demonstrated the highest adjusted HRs of 2.762 in alcoholic LC and 1.751 in non-alcoholic LC (all p < 0.001). In contrast, LC patients with hypertension and hyperlipidemia had a decreased risk of mortality. The six-year survival rates showed no difference between both study groups (p = 0.312). In conclusion, alcoholic LC patients were younger and had lower rates of concomitant comorbidities compared with non-alcoholic LC patients. However, all-cause mortality was not different between alcoholic and non-alcoholic LC patients.
In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied.
Summary and Conclusions The immune responses of 239 free-living children who received primary vaccination with 3 monthly doses of alum-precipitated DPT vaccine were analyzed on the basis of latent diphtheria immunity prior to vaccination. It was found that the latently diphtheria-immune group yielded significantly weaker pertussis agglutinin and tetanus antitoxin responses than the diphtheria non-immune group. The responses of the latently diphtheria-immune group showed the following characteristics: The magnitude of pertussis agglutinin formation was suppressed, with a mean titer ratio of 1:3.2 against the diphtheria non-immune group 1 mo after the third dose. During the period of observation, the interfered pertussis agglutinin response curve showed no tendency to cross the normal pertussis agglutinin response curve.Both speed and magnitude of tetanus antitoxin formation were heterologously interfered with, the most striking interference following the second dose (mean titer ratio 1:11.3). The interfered tetanus antitoxin response curve tends to cross the normal tetanus antitoxin response curve at their peaks.Weak but detectable interference of pertussis agglutinin and tetanus antitoxin responses occurs when there pre-exists the slightest degree of latent diphtheria immunity. As the degree of pre-existing diphtheria immunity increases, the interference intensifies. In our studies, a diphtheria antitoxin level of 0.01 u/ml represents that degree of immunity over and under which the intensity of interference differs significantly. A further graded increment of pre-existing diphtheria immunity above this level, however, does not result in proportional enhancement of interference. The significance of these observations is discussed.
Endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilatation (EPBD) are used for therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The postprocedure bleeding rate for EPBD is low in the normal population; however, this bleeding rate in a group of patients prone to bleeding, such as patients with end-stage renal disease, is not well-established. We therefore evaluated the post-EST and post-EPBD bleeding rate among hemodialysis (HD) patients based on data from Taiwan's National Health Insurance Research Database (NHIRD).The NHIRD entries for a population of 2 million were screened for patients who had a catastrophic illness card for HD between 1st January 2004 and 31st December 2011 and these patients were enrolled as research subjects. The rates of major gastrointestinal tract bleeding events appearing within 14 days after EST or EPBD were compared between HD and non-HD patients.A total of 3561 patients, over 18 years of age and without liver cirrhosis or hematologic diseases, underwent 3826 EST and 280 EPBD procedures during the 8 calendar years selected for our analysis. The total post-ERCP major bleeding rate was much higher in HD than in non-HD patients (8.64% vs. 2.16%, P < 0.0001). The rate of postprocedure major bleeding events was lower for non-HD patients who underwent EPBD than those who underwent EST (0.75% vs. 2.26%; P = 0.049), whereas the postprocedure major bleeding event rates were similar in HD patients who underwent either EPBD or EST (8.70% vs. 8.33%; P = 0.484).Post-ERCP, post-EST, and post-EPBD major bleeding rates were all higher in HD patients in this study. EPBD resulted in lower postprocedure major bleeding events than EST in the non-HD population, but it failed to provide the reduction in bleeding events needed to perform endoscopic hemostasis in HD patients.
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