TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Pirfenidone (5 methyl-1-phenyl-2(1H)-pyridone) is a novel anti-fibrotic agent, which has been shown to decrease collagen deposition in a variety of animal models in vivo, and recently in hepatic fibrosis also. At cellular level, we have recently demonstrated that pirfenidone is able to inhibit proliferation of hepatic stellate cells induced by platelet-derived growth factor, as well as collagen type I accumulation and alpha1(I) procollagen mRNA expression.', 'To evaluate if pirfenidone maintains its anti-fibrotic properties also when administered after the induction of hepatic damage and to further investigate the molecular mechanisms leading to the anti-fibrotic effect of pirfenidone.', 'Rats treated with dimethylnitrosamine (10 mg/kg) for 5 weeks received a liquid diet containing 0.5% pirfenidone starting from the third week. Pirfenidone treatment reduced the degree of liver injury, as determined by alanine aminotransferase values and necro-inflammatory score, which was associated with reduced hepatic stellate cells proliferation and collagen deposition. Treatment with dimethylnitrosamine increased transcripts levels for transforming growth factorbeta1, procollagen alpha1(I), tissue inhibitors of metalloproteinase-1 and matrix metalloproteinase-2 by 7-, 7-, 4- and 15-fold, respectively. Pirfenidone administration downregulated elevated levels of those transcripts by 50-60%, and this was associated with a 70% reduction in collagen deposition.\Question: Is the anti-fibrotic effect of pirfenidone in rat liver fibrosis mediated by downregulation of procollagen alpha1 ( I ) , TIMP-1 and MMP-2?

SOLUTION: (1) Pirfenidone is effective also if administered after the induction of the hepatic damage; (2) the anti-fibrotic effect of pirfenidone is mainly due to the reduced expression of profibrogenic procollagen alpha1(I) and TIMP-1, most likely through the downregulation of transforming growth factorbeta1 mRNA, and of matrix metalloproteinase-2, which is mainly implicated in the degradation of the normal extracellular matrix.

PROBLEM: Context: The aim of this exploratory study was to identify those factors associated with asthma control assessed according to GINA Guidelines.', '809 (56% female) subjects with asthma were recruited consecutively from both specialist and primary care centres. Asthma control was assessed over a 4-week follow-up period using a composite measure. A multivariate analysis was performed, in which asthma control was included as the dependent variable and several explanatory variables were included as independent variables.', 'Analysis performed on the whole population rendered gender (p=0.003), the type of physician (p<0.001), and age group (p<0.001), as significant factors associated with asthma control. In adults, gender (p=0.001), asthma severity (p<0.001), and type of physician (p<0.001) were significant, and only asthma severity was significant (p=0.043) in children.\Question: Are women , patients with severe asthma , and patients attended by primary care physicians , at higher risk of suffering from poorly controlled asthma?

SOLUTION: After model adjustment, we suggest that being female, suffering from more severe asthma, or being attended by a primary care physician, could pose a significantly higher risk of having poorly controlled asthma in adults.

PROBLEM: Context: The increased severity of disease associated with the NAP1 strain of Clostridium difficile has been attributed to mutations to the tcdC gene which codes for a negative regulator of toxin production. To assess the role of hyper-production of Toxins A and B in clinical isolates of Clostridium difficile, two NAP1-related and five NAP1 non-related strains were compared.', 'Sequencing was performed on tcdC, tcdR, and tcdE to determine if there were differences that might account for hyper-production of Toxin A and Toxin B in NAP1-related strains. Biological activity of Toxin B was evaluated using the HFF cell CPE assay and Toxin A biological activity was assessed using the Caco-2 Trans-membrane resistance assay.', 'Our results confirm that Toxin A and Toxin B production in NAP1-related strains and ATCC 43255 occurs earlier in the exponential growth phase compared to most NAP1-nonrelated clinical isolates. Despite the hyper-production observed in ATCC 43255 it had no mutations in tcdC, tcdR or tcdE. Analysis of the other clinical isolates indicated that the kinetics and ultimate final concentration of Toxin A and B did not correlate with the presence or lack of alterations in tcdC, tcdR or tcdE.\Question: Does truncation in the tcdC region of the Clostridium difficile PathLoc of clinical isolates predict increased biological activity of Toxin B or Toxin A?

SOLUTION:
Our data do not support a direct role for alterations in the tcdC gene as a predictor of hyperproduction of Toxin A and B in NAP1-related strains.