TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: Chemerin has been implicated to play opposing roles, either pro-inflammatory or anti-inflammatory, in various tissue inflammation processes primarily through the regulation of tissue recruitment of immune cells. However, the effect of chemerin in allergic asthma has not yet been explored. We sought to investigate the role of chemerin in the murine model of allergic asthma and explore the underlying mechanism.', 'We examined the effect of intranasal (i.n.) administration of chemerin during antigen challenge in murine models of asthma. Moreover, we examined whether administration of CCL2 or bone marrow-derived dendritic cells (BMDCs) transfer reversed the effects of chemerin on ovalbumin-induced asthma. We finally examined the effect of chemerin on CCL2 expression in activated lung epithelial cells in vitro.', 'The administration of chemerin attenuated allergic airway inflammation and airway hyperreactivity during antigen challenge. Chemerin treatment caused significant decreases in BALF CD4(+) T-cell accumulation and mRNA expression of Th2-attracting chemokines, CCL17 and CCL22, which was accompanied by significantly decreased BALF CD11c(+) CD11b(+) inflammatory DC accumulation and CCL2 production. Furthermore, airway administration of exogenous CCL2 or adoptive transfer of CD11c(+) CD11b(+) BMDCs abrogated the suppressive effects of chemerin on allergic asthma. Finally, in vitro study showed that chemerin inhibited CCL2 secretion by low-dose LPS-stimulated lung epithelial cells, which led to decreased chemotaxis of BMDCs.
Answer: Our study demonstrates that chemerin plays a protective role in allergic asthma by suppressing airway recruitment of inflammatory CD11c(+) CD11b(+) DCs through the inhibition of CCL2 secretion by active lung epithelial cells.

SOLUTION: Does chemerin suppress murine allergic asthma by inhibiting CCL2 production and subsequent airway recruitment of inflammatory dendritic cells?

PROBLEM: Context: Islet cell transplantation can cure type 1 diabetes (T1D), but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.', 'Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG) induction and tacrolimus plus mycophenolate mofetil (MMF) maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively) and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively). Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.
Answer: In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular islet autoreactivity may be required. Monitoring cellular immune reactivity can be useful to identify factors influencing graft survival and to assess efficacy of immunosuppression.

SOLUTION: Does cellular islet autoimmunity associate with clinical outcome of islet cell transplantation?

PROBLEM: Context: There is great variability for the type of anaesthesia used during TAVI, with no clear consensus coming from comparative studies or guidelines. We sought to detect regional differences in the anaesthetic management of patients undergoing transcatheter aortic valve implantation (TAVI) in Europe and to evaluate the relationship between type of anaesthesia and in-hospital and 1 year outcome.', 'Between January 2011 and May 2012 the Sentinel European TAVI Pilot Registry enrolled 2807 patients treated via a transfemoral approach using either local (LA-group, 1095 patients, 39%) or general anaesthesia (GA-group, 1712 patients, 61%).', 'A wide variation in LA use was evident amongst the 10 participating countries. The use of LA has increased over time (from a mean of 37.5% of procedures in the first year, to 57% in last 6 months, p<0.01). MI, major stroke as well as in-hospital death rate (7.0% LA vs 5.3% GA, p=0.053) had a similar incidence between groups, confirmed in multivariate regression analysis after adjusting for confounders. Dividing our population in tertiles according to the Log-EuroSCORE we found similar mortality under LA, whilst mortality was higher in the highest risk tertile under GA. Survival at 1 year, compared by Kaplan-Meier analysis, was similar between groups (log-rank: p=0.1505).
Answer: Selection of anaesthesia appears to be more influenced by national practice and operator preference than patient characteristics. In the absence of an observed difference in outcomes for either approach, there is no compelling argument to suggest that operators and centres should change their anaesthetic practice.

SOLUTION:
Do local and general anaesthesia influence outcome of transfemoral aortic valve implantation?