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: Natriuretic peptide (NP) levels are routinely employed as useful diagnostic and prognostic tools in the evaluation of patients with heart failure (HF). As hospitalization is the major consumer of healthcare resources, the prognostic power of admission NPs with regard to the duration of hospitalization deserves further investigation.', 'We assessed retrospectively the association between NP values sampled shortly following unplanned admission and the duration of hospitalization in 2978 patients admitted to a cardiology department. Duration of hospitalization (hours) and survival were determined by interrogation of the electronic medical records system. Associations with peptide levels were estimated using regression models and receiver operating characteristic (ROC) analysis. The results demonstrate a significant positive relationship between NP levels and the duration of hospitalization, after adjusting for age (P < 0.001). The median duration of hospitalization for the lowest BNP and NT-proBNP quintiles were 80 and 97 h, respectively, vs. 224.5 and 236 h for the highest quintiles. Using cut-off levels of 115 pmol/L for BNP and 390 pmol/L for NT-proBNP, the peptides have a positive predictive value of 78% and 85% for a stay >4 days. During follow-up, NP levels were strongly predictive of all-cause mortality.
Answer: The results quantify the strong relationship between NP levels taken following an unplanned admission to a cardiology department and the duration of hospitalization. This information permits improved identification of a patient population likely to require a prolonged hospital stay and consume more healthcare resources. Such patients may require a more aggressive diagnostic, treatment, and management strategy.

SOLUTION: Do natriuretic peptide levels taken following unplanned admission to a cardiology department predict the duration of hospitalization?

PROBLEM: Context: Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) are controversial and mostly based on a heterologous rat Nb2 cell bioassay. Biological activity of bbPRL observed in vitro but not in vivo may be due to its high molecular weight, preventing its passage through capillary barrier. Alternatively, bbPRL bioactivity may differ depending on the prolactin (PRL) receptor (PRLR) species specificity.', 'The objective of the study was to characterize the bioactivity of bbPRL in a homologous bioassay: Ba/F-3 cells stably expressing the human PRLR.', "Chromatography-purified bbPRL from macroprolactinemic individuals (group I, n = 18) and monomeric PRL from hyperprolactinemic patients without macroprolactinemia (group II, n = 5) were tested in Nb2 and Ba/F-LLP bioassays. Both groups were followed up at the neuroendocrinology outpatients' clinic.", 'Biological activity of bbPRL presented in the two bioassays was measured.', 'In group I, no patient had hypogonadism. Mean ratio bioactivity to immunoactivity of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 of the 18 samples tested in Ba/F-LLP assay. In group II, three patients had galactorrhea and all five had hypogonadism. Mean ratio bioactivity to immunoactivity of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay.
Answer: Whereas both bioassays achieve similar results with respect to monomeric PRL activity, our results indicate that the activity displayed by bbPRL toward the rat receptor may be inappropriate because it is not observed in the human PRLR-mediated assay, consistent with the apparent absence of bioactivity in vivo.

SOLUTION: Does human macroprolactin display low biological activity via its homologous receptor in a new sensitive bioassay?

PROBLEM: Context: It has been shown that sarcolemmal rupture can occur during reenergization in cardiomyocytes in which previous ischemia has induced sarcolemmal fragility by calpain-dependent hydrolysis of structural proteins. We tested the hypothesis that attenuated calpain activation contributes to the protection against reperfusion-induced cell death afforded by ischemic preconditioning (IPC), and investigated the involvement of protein kinase A (PKA) in this effect.', 'Calpain activity and degradation of different structural proteins were studied along with the extent of necrosis in isolated rat hearts submitted to 60 min of ischemia and 30 min of reperfusion with or without previous IPC (two cycles of 5 min ischemia-5 min reperfusion), and the ability of different treatments to mimic or blunt the effects of IPC were analyzed.', 'IPC accelerated ATP depletion and rigor onset during ischemia but reduced LDH release during reperfusion by 69% (P<0.001). At the end off reperfusion, calpain activity was reduced by 66% (P<0.001) in IPC, and calpain-dependent degradation of sarcolemmal proteins was attenuated. Addition of the calpain inhibitor MDL-28170 mimicked the effects of IPC on protein degradation and reduced LDH release by 48% (P<0.001). The effects of IPC on calpain, alpha-fodrin, and LDH release were blunted by the application of the PKA inhibitor H89 or alprenolol during IPC, while transient stimulation of PKA with CPT-cAMP or isoproterenol before ischemia attenuated calpain activation, alpha-fodrin degradation, and markedly reduced LDH release (P<0.001). In hearts exposed to Na(+)-free perfusion, IPC attenuated calpain activation by 67% (P<0.001) and reduced by 56% (P<0.001) LDH release associated to massive edema occurring during Na(+) readmission without modifying its magnitude.
Answer: These results are consistent with PKA-dependent attenuation of calpain-mediated degradation of structural proteins being an end-effector mechanism of the protection afforded by IPC.

SOLUTION:
Does ischemic preconditioning attenuate calpain-mediated degradation of structural proteins through a protein kinase A-dependent mechanism?