Effect of IL-4 and IL-13 on IFN-γ-induced production of nitric oxide in mouse macrophages infected with herpes simplex virus type 2

AbstractInterleukin (IL)-4 and IL-13 share a wide range of activities. Prominent among these is the ability to antagonize many interferon (IFN)-γ-induced activities. Here we demonstrate that IL-4 and IL-13 totally abrogate IFN-γ-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA and protein synthesis in a murine macrophage cell line. IFN-γ-treated cells infected with herpes simplex virus type 2 (HSV-2) or costimulated with tumor necrosis factor (TNF)-α showed an enhanced reactivity, which was only partially reduced by IL-4/13. The results indicate that IL-4 and IL-13 function by intervening with a step prior to iNOS transcription by antagonizing IFN-γ-induced signal(s) without counteracting synergistic virus- or TNF-α-induced signals. The beneficial effect of a sustained NO production in foci of virus infection is suggested

Detecting Determinacy in Prolog Programs: 22nd International Conference, ICLP 2006, Seattle, WA, USA, August 17-20, 2006. Proceedings

In program development it is useful to know that a call to a Prolog program will not inadvertently leave a choice-point on the stack. Determinacy inference has been proposed for solving this problem yet the analysis was found to be wanting in that it could not infer determinacy conditions for programs that contained cuts or applied certain tests to select a clause. This paper shows how to remedy these serious deficiencies. It also addresses the problem of identifying those predicates which can be rewritten in a more deterministic fashion. To this end, a radically new form of determinacy inference is introduced, which is founded on ideas in ccp, that is capable of reasoning about the way bindings imposed by a rightmost goal can make a leftmost goal deterministic

Return to the workforce following first hospitalization for heart failure: a Danish nationwide cohort study

Background: Return to work is important financially, as a marker of functional status and for self-esteem in patients developing chronic illness. We examined return to work after first heart failure (HF) hospitalization. Methods: By individual-level linkage of nationwide Danish registries, we identified 21455 patients of working age (18-60 years) with a first HF hospitalization in the period of 1997-2012. Of these 11880 (55%) were in the workforce prior to HF hospitalization and comprised the study population. We applied logistic regression to estimate odds ratios (OR) for associations between age, sex, length of hospital stay, level of education, income, comorbidity and return to work. Results: One year after first HF hospitalization, 8040 (67.7%) returned to the workforce, 2981 (25.1%) did not, 805 (6.7%) died and 54 (0.5%) emigrated. Predictors of return to work included younger age (18-30 vs. 51-60 years, OR 3.12; 95% CI 2.42-4.03), male sex (OR 1.22 [1.18-1.34]) and level of education (long-higher vs. basic school OR 2.06 [1.63-2.60]). Conversely, hospital stay >7 days (OR 0.56 [0.51-0.62]) and comorbidity including history of stroke (OR 0.55 [0.45-0.69]), chronic kidney disease (OR 0.46 [0.36-0.59]), chronic obstructive pulmonary disease (OR 0.62 [0.52-0.75]), diabetes (OR 0.76 [0.68-0.85]) and cancer (OR 0.49 [0.40-0.61]) were all significantly associated with lower chance of return to work. Conclusions: Patients in the workforce prior to HF hospitalization had low mortality but high risk of detachment from the workforce one year later. Young age, male sex, and higher level of education were predictors of return to work

Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction. A report from the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial (I-Preserve)

Background—In patients with HF and preserved ejection fraction (HFpEF), little is known about the characteristics of and outcomes in those with and without diabetes. Methods—We examined clinical and echocardiographic characteristics and outcomes in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), according to history of diabetes. Cox regression models were used to estimate hazard ratios (HR) for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. Results—Overall, 1134 of 4128 patients (27%) had diabetes. Compared to those without diabetes, they were more likely to have a history of myocardial infarction (28% vs. 22%), higher BMI (31kg/m2 vs. 29kg/m2), worse Minnesota living with HF score (48 vs. 40), higher median NT-proBNP concentration (403 vs 320 pg/ml; all p<0.01), more signs of congestion but no significant difference in LVEF. Patients with diabetes had a greater left ventricular (LV) mass and left atrial area than patients without diabetes. Doppler E wave velocity (86 vs 76 cm/sec, p<0.0001) and the ratio of E/e' (11.7 vs 10.4, p=0.010) were higher in patients with diabetes. Over a median follow-up of 4.1 years, cardiovascular death or HF hospitalization occurred in 34% of patients with diabetes vs. 22% of those without diabetes; adjusted HR 1.75 (95% CI 1.49-2.05) and 28% vs. 19% of patients with and without diabetes died; adjusted HR 1.59 (1.33-1.91). Conclusions—In HFpEF, patients with diabetes have more signs of congestion, worse quality of life, higher NT-proBNP levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes on outcomes in HFPEF, and whether they are modifiable

Rate and predictors for non-attendance of patients undergoing hospital outpatient treatment for chronic diseases: a register-based cohort study.

Failure to keep medical appointments results in inefficiencies and, potentially, in poor outcomes for patients. The aim of this study is to describe non-attendance rate and to investigate predictors of non-attendance among patients receiving hospital outpatient treatment for chronic diseases. We conducted a historic, register-based cohort study using data from a regional hospital and included patients aged 18 years or over who were registered in ongoing outpatient treatment courses for seven selected chronic diseases on July 1, 2013. A total of 5895 patients were included and information about their appointments was extracted from the period between July 1, 2013 and June 30, 2015. The outcome measure was occurrence of non-attendance. The associations between non-attendance and covariates (age, gender, marital status, education level, occupational status, specific chronic disease and number of outpatient treatment courses) were investigated using multivariate logistic regression models, including mixed effect. During the two-year period, 35% of all patients (2057 of 5895 patients) had one or more occurrences of non-attendance and 5% of all appointments (4393 of 82,989 appointments) resulted in non-attendance. Significant predictors for non-attendance were younger age (OR 4.17 for 18 ≤ 29 years as opposed to 80+ years), male gender (OR 1.35), unmarried status (OR 1.39), low educational level (OR 1.18) and receipt of long-term welfare payments (OR 1.48). Neither specific diseases nor number of treatment courses were associated with a higher non-attendance rate. Patients undergoing hospital outpatient treatments for chronic diseases had a non-attendance rate of 5%. We found several predictors for non-attendance but undergoing treatment for several chronic diseases simultaneously was not a predictor. To reduce non-attendance, initiatives could target the groups at risk. This study was approved by the Danish Data Protection Agency (Project ID 18/35695 )