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.

Q: Context: Alterations in epigenetic processes are frequently noted in human disease. These epigenetic processes involve methylation of DNA and post-translational modifications of histones. It is well established that in particular histone methylation plays a key role in gene transcription. In this study, we have investigated the relationship between triple methylation of lysine 27 in histone H3 (H3K27Me3) modifications and atherosclerotic plaque stage.', '28 peri-renal aortic tissue patches covering the entire spectrum of atherosclerotic plaque development were evaluated by immunohistochemistry for the levels of H3K27Me3, EZH2, JMJD3 and BMI1.', 'The results of our studies are in support of a reduction in global levels of the H3K27Me3 modification in vessels with advanced atherosclerotic plaques. This reduction in H3K27Me3 levels is not accompanied by alterations in global levels of the corresponding histone methyltransferase EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2). Likewise no alterations in global levels of BMI1, a component of the PRC1 complex, which binds to H3K27Me3-modified histones or the global expression levels of the histone demethylase JMJD3, which removes the methyl marks on H3K27, were observed.
Answer: Together, our data show that in atherosclerosis development alterations in global levels of H3K27Me3 occur. The reduction in the number of nuclei in the tunica media that display the repressive H3K27Me3 mark in vessels with advanced atherosclerosis plaques therefore could be a reflection of the dynamic pattern of smooth muscle cell differentiation and proliferation associated with atherosclerotic disease.

A: Are global histone H3 lysine 27 triple methylation levels reduced in vessels with advanced atherosclerotic plaques?
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Q: Context: After ingestion of phosphatidylcholine, l-carnitine or betaine, trimethylamine-N-oxide (TMAO) is formed by gut microbiota and liver enzymes. Elevated TMAO plasma levels were associated with increased cardiovascular risk and other diseases. Also betaine and choline itself were recently associated with increased cardiovascular risk.', 'A newly developed LC-HRMS method was applied to measure the plasma concentrations of TMAO, betaine and choline in a cohort of 339 patients undergoing coronary angiography for the evaluation of suspected coronary artery disease.', "Betaine concentrations in males were significantly higher than in females (42.0 vs. 35.9\xa0μmol/L; p\xa0<\xa00.001). Plasma concentrations of TMAO but not of betaine or choline were higher in patients with diabetes compared to euglycemic patients (2.39 vs. 0.980\xa0μmol/L; p\xa0=\xa00.001) as well as in patients with metabolic syndrome as compared to patients without metabolic syndrome (2.37 vs. 1.43\xa0μmol/L; p\xa0=\xa00.002). Plasma concentrations of TMAO or choline increased significantly with decreasing renal function (Spearman's rho:\xa0-0.281; p\xa0<\xa00.001). However, plasma levels of TMAO or betaine were associated with neither a history of myocardial infarction nor the angiographically assessed presence of coronary heart disease, nor incident cardiovascular events during 8 years of follow-up. Plasma levels of choline were significantly lower in patients with a history of acute myocardial infarction as compared to those without such history (10.0 vs. 10.8\xa0μmol/L; p\xa0=\xa00.045).
Answer: Plasma levels of TMAO are confounded by impaired kidney function and poor metabolic control but are not associated with the history, presence or incidence of symptoms or events of coronary heart disease.

A: Are plasma levels of trimethylamine-N-oxide confounded by impaired kidney function and poor metabolic control?
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Q: Context: Fibrinogen concentrate is increasingly considered as a hemostatic agent for trauma patients experiencing bleeding. Placing a venous access is sometimes challenging during severe hemorrhage. Intraosseous access may be considered instead. Studies of intraosseous infusion of coagulation factor concentrates are limited. We investigated in vivo recovery following intraosseous administration of fibrinogen concentrate and compared the results with intravenous administration.', 'This study was performed on 12 pigs (mean [SD] body weight, 34.1 [2.8] kg). Following controlled blood loss (35 mL/kg) and fluid replacement with balanced crystalloid solution, intraosseous (n = 6) administration of fibrinogen concentrate (80 mg per kilogram of bodyweight) in the proximal tibia was compared with intravenous (n = 6) administration of the same dose (fibrinogen infusion time approximately 5 minutes in both groups). The following laboratory parameters were assessed: blood cell count, prothrombin time index, activated partial thromboplastin time, and plasma fibrinogen concentration (Clauss assay). Coagulation status was also assessed by thromboelastometry.', 'All tested laboratory parameters were comparable between the intraosseous and intravenous groups at baseline, hemodilution, and 30 minutes after fibrinogen concentrate administration. In vivo recovery of fibrinogen was also similar in the two groups (89% [23%] and 91% [22%], respectively). There were no significant between-group differences in any of the thromboelastometric parameters. Histologic examination indicated no adverse effects on the tissue surrounding the intraosseous administration site.
Answer: This study suggests that intraosseous administration of fibrinogen concentrate results in a recovery of fibrinogen similar to that of intravenous administration. The intraosseous route of fibrinogen concentrate could be a valuable alternative in situations where intravenous access is not feasible or would be time consuming.

A:
Is recovery of fibrinogen concentrate after intraosseous application equivalent to the intravenous route in a porcine model of hemodilution?
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