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: Assessment of the activity of thioridazine towards Mycobacterium tuberculosis (Mtb), in\xa0vitro and in\xa0vivo as a single drug and in combination with tuberculosis (TB) drugs.', 'The in\xa0vitro activity of thioridazine as single drug or in combination with TB drugs was assessed in terms of MIC and by use of the time-kill kinetics assay. Various Mtb strains among which the Beijing genotype strain BE-1585 were included. In\xa0vivo, mice with TB induced by BE-1585 were treated with a TB drug regimen with thioridazine during 13 weeks. Therapeutic efficacy was assessed by the change in mycobacterial load in the lung, spleen and liver during treatment and 13 weeks post-treatment.', 'In\xa0vitro, thioridazine showed a concentration-dependent and time-dependent bactericidal activity towards both actively-replicating and slowly-replicating Mtb. Thioridazine at high concentrations could enhance the activity of isoniazid and rifampicin, and in case of isoniazid resulted in elimination of mycobacteria and prevention of isoniazid-resistant mutants. Thioridazine had no added value in combination with moxifloxacin or amikacin. In mice with TB, thioridazine was poorly tolerated, limiting the maximum tolerated dose (MTD). The addition of thioridazine at the MTD to an isoniazid-rifampicin-pyrazinamide regimen for 13 weeks did not result in enhanced therapeutic efficacy.
Answer: Thioridazine is bactericidal towards Mtb in vitro, irrespective the mycobacterial growth rate and results in enhanced activity of the standard regimen. The in vitro activity of thioridazine in potentiating isoniazid and rifampicin is not reflected by improved therapeutic efficacy in a murine TB-model.

SOLUTION: Is enhancement of in vitro activity of tuberculosis drugs by addition of thioridazine reflected by improved in vivo therapeutic efficacy?

PROBLEM: Context: Central giant cell lesion (CGCL) and giant cell tumour (GCT) are bone lesions that share similar microscopic features. Recently, it was reported that 90% of bone GCT exhibit either p.Gly34 Trp or p.Gly34 Leu in H3F3A, one of two genes for histone H3.3 located on chromosome 1. We aimed to test whether sporadic CGCL of the jaws share the H3F3A mutations reported in GCT of other bones.', 'Nine samples of CGCL of the jaws were included in the study, and mutations were assessed by direct sequencing.', 'None of the CGCL samples presented the recurrent p.Gly34 Trp or p.Gly34 Leu mutations in the H3F3A gene.
Answer: On the basis of our findings, H3F3A p.Gly34 Trp or p.Gly34 Leu mutations are not a frequent event in CGCL. If these alterations are confirmed to be exclusive of GCT, the assessment of H3F3A mutations may help in the differential diagnosis of GCT and CGCL of the jaws.

SOLUTION: Is the highly prevalent H3F3A mutation in giant cell tumours of bone shared by sporadic central giant cell lesion of the jaws?

PROBLEM: Context: Intravenous oxygen infusions have been introduced in complementary medicine for treatment of atherosclerosis and inflammatory diseases. As atherosclerosis and inflammation are causally related to oxidative stress and as intravenous supply with oxygen causes oxidative stress, it was suggested that the clinical success of intravenous oxygen therapy is biochemically based on an enhancement of endogenous antioxidative mechanisms. The anti-atherogenic enzyme paraoxonase-1 (PON1) is is part of this system.', 'To evaluate the effect of repeated intravenous oxygen infusions on serum PON1 activity.', 'A total of 45 patients were treated with intravenous oxygen. During treatment oxygen dosage was increased from 15 to 50 ml (1-2 ml/min). Before treatments 1 and 10 blood was obtained for measurement of PON1 activities. From 20 patients blood was additionally obtained after 20 days of treatment and 2 weeks post treatment. Serum PON1 activity was measured spectrophotometrically using the synthetic substrates paraoxon, phenylacetate, and p-nitrophenyl-acetate.', 'Using the substrate paraoxon PON1 activity significantly increased by 38% above basal levels 24 hours after intravenous oxygen infusion 9 (p < 0.001). Adverse effects were not observed.
Answer: Treatments with intravenous oxygen infusions evoke an adaptation to oxidative stress by an increase of serum PON1 activity. In this regard, a potential molecular mechanism has been found, that explains the protecting effects of intravenous oxygen therapy against oxidative stress and its consequences. PON1 activity is proposed to be an appropriate parameter for monitoring the success of this kind of oxygen therapy.

SOLUTION:
Does [ Intravenous oxygen therapy increase the activity of the antioxidative and antiatherogenic serum enzyme paraoxonase 1 ]?