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: Heat shock protein-27 (HSP-27) belongs to the group of small heat shock proteins that become induced in response to various pathologic conditions. HSP-27 has been shown to protect cells and subcellular structures, particularly mitochondria, and serves as a carrier for estradiol. It is a reliable marker for tissues affected by oxidative stress. Oxidative stress and related cellular defence mechanisms are currently thought to play a major role during experimentally induced epileptic neuropathology. We addressed the question whether HSP-27 becomes induced in the neocortex resected from patients with pharmacoresistant epilepsy.', "Human epileptic temporal neocortex was obtained during neurosurgery, and control tissue was obtained at autopsy from subjects without known neurologic diseases. The tissues were either frozen for Western blot analysis or fixed in Zamboni's fixative for the topographic detection of HSP-27 at the cellular level by means of immunohistochemistry.", 'HSP-27 was highly expressed in all epilepsy specimens and in the cortex of a patient who died in the final stage of multiple sclerosis (positive control), whereas only low amounts of HSP-27 were detectable in control brains. In epilepsy patients, HSP-27 was present in astrocytes and in the walls of blood vessels. The intracortical distribution patterns varied strongly among the epilepsy specimens.
Answer: These results demonstrate that HSP-27 becomes induced in response to epileptic pathology. Although the functional aspects of HSP-27 induction during human epilepsy have yet to be elucidated, it can be concluded that HSP-27 is a marker for cortical regions in which a stress response has been caused by seizures.

SOLUTION: Is heat shock protein-27 upregulated in the temporal cortex of patients with epilepsy?

PROBLEM: Context: Nonviral vectors based on polyethylenimine (PEI) usually contain an excess of PEI that is not complexed to DNA. Since unbound PEI contributes to cellular and systemic toxicity, purification of polyplexes from unbound PEI is desirable.', 'Size exclusion chromatography (SEC) was used to purify PEI polyplexes of free PEI. Transfection properties of purified polyplexes and the effect of free PEI on gene delivery were studied in vitro and in vivo after systemic application into mice.', 'SEC did not change the size and zeta-potential of polyplexes. Independent of the amount of PEI used for complex formation, purified PEI polyplexes had the same final PEI nitrogen/DNA phosphate ratio of 2.5. Notably, purified PEI polyplexes demonstrated low cellular and systemic toxicity. High transfection efficiency was achieved with purified polyplexes at high DNA concentrations (8-15 microg/ml). At low DNA concentrations (2-4 microg/ml) gene transfer with purified particles was less efficient than with polyplexes containing free PEI both in vitro and in vivo. Mechanistic studies showed that free PEI partly blocked cellular association of DNA complexes but was essential for the following intracellular gene delivery. Adding free PEI to cells treated with purified particles with a delay of up to 4 h resulted in significantly enhanced transfection efficiency compared with non-purified particles or purified particles without free PEI.
Answer: This study presents an efficient method to remove free PEI from PEI polyplexes by SEC. Our results from transfection experiments demonstrate that free PEI substantially contributes to efficient gene expression but also mediates toxic effects in a dose-dependent manner. Purified polyplexes without free PEI have to be applied at increased concentrations to achieve high transfection levels, but exhibit a greatly improved toxicity profile.

SOLUTION: Does purification of polyethylenimine polyplexes highlight the role of free polycations in gene transfer?

PROBLEM: Context: The COMFORT behaviour scale (COMFORT-B scale) is widely used in paediatric intensive care units to assess young children's pain and distress. It is also used to assess the impact of treatment interventions, but little is known on the scale's sensitivity to detect changes between before and after measurements following an intervention. This study explored the sensitivity to change of the COMFORT-B scale.", 'COMFORT-B scores, originally and prospectively collected as part of standard care, were retrieved from the digital patient data management system. We analysed scores obtained in 747 paired observations, i.e., before and after a pharmacological intervention in 180 paediatric intensive care patients between September 2009 and September 2010.', 'The mean scores before and after an intervention were 20.0 [standard deviation (SD) 3.7] and 14.1 (SD 4.7), respectively. Multilevel regression analysis showed a 6-point mean decline after an intervention (p\u2009<\u20090.0001). The magnitude of this decline was not statistically significantly related to number and type of interventions or time between assessments. In almost three-quarters of cases (74%), the COMFORT-B score dropped to below 17 after a pharmacological intervention, indicating good responsiveness.
Answer: This is the first study demonstrating that the COMFORT-B scale detects treatment-related changes in pain or distress intensity. This implies that COMFORT-B assessments can effectively guide analgesic and sedation treatment in critically ill children.

SOLUTION:
Does the COMFORT behaviour scale detect clinically meaningful effects of analgesic and sedative treatment?