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: Prostaglandin D2 (PGD2) and cysteinyl leukotrienes (cysLTs) are lipid mediators derived from mast cells, which activate TH2 cells. The combination of PGD2 and cysLTs (notably cysteinyl leukotriene E4 [LTE4]) enhances TH2 cytokine production. However, the synergistic interaction of cysLTs with PGD2 in promoting TH2 cell activation is still poorly understood. The receptors for these mediators are drug targets in the treatment of allergic diseases, and hence understanding their interaction is likely to have clinical implications.', 'We aimed to comprehensively define the roles of PGD2, LTE4, and their combination in activating human TH2 cells and how such activation might allow the TH2 cells to engage downstream effectors, such as neutrophils, which contribute to the pathology of allergic responses.', 'The effects of PGD2, LTE4, and their combination on human TH2 cell gene expression were defined by using a microarray, and changes in specific inflammatory pathways were confirmed by means of PCR array, quantitative RT-PCR, ELISA, Luminex, flow cytometry, and functional assays, including analysis of downstream neutrophil activation. Blockade of PGD2 and LTE4 was tested by using TM30089, an antagonist of chemoattractant receptor-homologous molecule expressed on TH2 cells, and montelukast, an antagonist of cysteinyl leukotriene receptor 1.', 'PGD2 and LTE4 altered the transcription of a wide range of genes and induced diverse functional responses in TH2 cells, including cell adhesion, migration, and survival and cytokine production. The combination of these lipids synergistically or additively enhanced TH2 responses and, strikingly, induced marked production of diverse nonclassical TH2 inflammatory mediators, including IL-22, IL-8, and GM-CSF, at concentrations sufficient to affect neutrophil activation.
Answer: PGD2 and LTE4 activate TH2 cells through different pathways but act synergistically to promote multiple downstream effector functions, including neutrophil migration and survival. Combined inhibition of both PGD2 and LTE4 pathways might provide an effective therapeutic strategy for allergic responses, particularly those involving interaction between TH2 cells and neutrophils, such as in patients with severe asthma.

SOLUTION: Do prostaglandin D2 and leukotriene E4 synergize to stimulate diverse TH2 functions and TH2 cell/neutrophil crosstalk?

PROBLEM: Context: Anemia is an established adverse risk factor in cardiovascular disease. However, the effect of preoperative anemia is not well defined in heart surgery. This study evaluates the effect of preoperative anemia on early clinical outcomes in patients undergoing cardiac surgery.', 'A retrospective, observational, cohort study of prospectively collected data was undertaken on 7,738 consecutive patients undergoing heart surgery between April 2003 and February 2009. Of these, 1,856 patients with preoperative anemia were compared to 5,882 patients without anemia (control group). According to the World Health Organization, anemia was defined as hemoglobin level<13 g/dl for men and <12 g/dl for women. Selection bias not controlled by multivariable methods was assessed with propensity-adjustment method.', 'Overall mortality was 2.1%. Preoperative anemia was associated with tripling in the risk of death (4.6% vs 1.5%, p<0.0001) and postoperative renal dysfunction (18.5% vs 6.5%, p<0.0001). There was also a significant difference between the anemic and non-anemic group in the risk of postoperative stroke (1.9% vs 1.1%, p=0.008), atrial fibrillation (36.7% vs 33%, p=0.003) and length of hospital stay>7 days (54% vs 36.7%, p<0.0001). In propensity-adjusted, multivariable logistic regression, preoperative anemia was an independent predictor of mortality (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.02 to 2.03), postoperative renal dysfunction (OR 1.73, 95% CI 1.43 to 2.1) and length of hospital stay>7 days (OR 1.3, 95% CI 1.15 to 1.47).
Answer: In patients undergoing heart surgery, preoperative anemia is associated with an increased risk of mortality and postoperative morbidity.

SOLUTION: Does preoperative anemia increase mortality and postoperative morbidity after cardiac surgery?

PROBLEM: Context: This study was designed to examine the course of psychological distress and pain from study entry to death in 59 women with metastatic breast cancer participating in a randomized trial of the effects of group psychotherapy on psychosocial outcomes and survival. It was hypothesized that psychological distress would increase significantly before death independent of changes in pain.', 'Data were collected as part of a larger study (N = 125). Analyses were based on data from a subset of women who had died and for whom we had data from at least three assessments. Mean levels of mood, trauma symptoms, depression symptoms, well-being, and pain over three time points were examined: at baseline (T1), the second-to-last assessment before death (T2), and the last assessment before death (T3).', 'Results indicate that while psychological distress remained relatively constant or declined from T1 to T2, means on all measures significantly changed in the hypothesized direction from T2 to T3. Neither self-reported pain, nor the passage of time, appeared to account for these changes. Additionally, participation in group psychotherapy did not have a significant impact on this change in distress proximal to death.
Answer: Results suggest that specialized end-stage clinical interventions are particularly needed for cancer patients as they approach death. Moreover, intervention studies for patients with deteriorating illnesses may need to take this "spike" in psychological distress and pain proximal to death into account to avoid Type II errors in evaluations of psychological outcomes.

SOLUTION:
Do psychological distress and pain significantly increase before death in metastatic breast cancer patients?