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: Tumor necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine. Recently, the G-308A polymorphism of the TNF-alpha gene has been associated with modified gene expression and increased TNF-alpha production in the -308A allele. We evaluated its influence on the incidence and clinical course of membranous glomerulonephritis.', 'We studied 53 patients with biopsy-proven primary membranous glomerulonephritis followed up for 5.7 +/- 4.9 years. 100 volunteers were analyzed as controls. According to the slope of the curve of reciprocal serum creatinine against time, group A (slow progressors, n = 35) and group B (fast progressors, n = 18) were defined. TNF-alpha G-308A polymorphism was determined by polymerase chain reaction amplification.', 'The frequency of the A-allele (associated with higher TNF-alpha levels) was significantly higher in patients than control subjects (patients: G-allele: 0.66, A-allele: 0.34; controls: G-allele 0.85, A-allele 0.15, p < 0.001). Similarly, the genotype distribution differed significantly between our study and control populations (patients: GG-genotype: 41.5%, GA: 49.1%, AA 9.4%; controls: GG: 71%, GA: 27%, AA 2%, p = 0.001). Age, renal function, proteinuria and blood pressure were similar at the time of renal biopsy between patients with different genotypes (NS). There was also a tendency towards an overpresentation of the A-allele in group B indicating a possible impact on the progression of membranous nephropathy, but a significance was not reached. Furthermore, no impact on renal survival in the Kaplan- Meier analysis was detected (NS).
Answer: Our results suggest that TNF-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis.

SOLUTION: Is tumor necrosis factor-alpha gene G-308A polymorphism a risk factor for the development of membranous glomerulonephritis?

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: Cardiopulmonary resuscitation (CPR) is now widely used as a treatment for ventricular fibrillation, though numerous studies have shown the outcome of standard CPR to be dismal. Alternative methods of CPR, including interposed abdominal compression, constant aortic occlusion, and the use of intrathoracic pressure regulator, have been shown to increase cardiac output and affect the mortality rate of CPR.', 'Here we suggest the Trendelenburg position as yet another method of increasing cardiac output and therefore improving the effectiveness of chest compressions. We hypothesized that the use of the Trendelenburg position during CPR would increase cardiac output as measured by carotid blood flow.', 'We anaesthetized six pigs and measured their pre-arrest carotid flow rate for two minutes. We then induced ventricular fibrillation in those pigs and performed open-chest CPR on them. Post-arrest carotid blood flow was measured for two minutes each at 0 (supine position), 10, 20, and 30 degrees of head-down tilt in each pig. The mean carotid flow for each degree of tilt was compared to mean carotid flow at 0 degrees of tilt using a paired student t-test.', 'We found an increase of up to 1.4-fold in carotid blood flow during CPR in the Trendelenburg position, though only 20 and 30 degrees of Trendelenburg showed a statistically significant increase from the 0 degrees of tilt in pigs.
Answer: The Trendelenburg position can lead to increased blood flow through the carotid arteries during CPR in this pig model. Future studies should investigate whether this increased blood flow through the carotid arteries leads to improved brain perfusion and better neurologic outcomes.

SOLUTION:
Does use of the trendelenburg position in the porcine model improve carotid flow during cardiopulmonary resuscitation?