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: Biliary tract obstruction is a common clinical problem. In this study, we attempted to understand the change in intestinal glucose absorption after biliary tract obstruction.', 'Experimental models of murine biliary duct ligation and external biliary drainage were established. Murine intestinal mucosal glucose absorption was examined with Ussing chambers according to the increase in the short-circuit current in\xa0vitro and blood glucose measurement after oral glucose in\xa0vivo. The protein expression of the sodium-glucose cotransporter (SGLT1) and the facilitated glucose transporter, member 2 (GLUT2) was analyzed by Western blot and immunohistochemistry.', 'The results from Ussing chamber experiments showed that duodenal mucosal glucose absorption levels were significantly higher in biliary duct ligation and biliary drainage mice than those in normal control mice at 1 and 2\xa0weeks after the operation. Gastrointestinal bile acid administration almost reversed the elevated duodenal mucosal glucose absorption to the normal level in biliary drainage mice. The results from the experiments in\xa0vivo further confirmed that the glucose absorption increased in biliary duct ligation and biliary drainage mice. The protein expression levels of SGLT1 in the duodenal mucosae of both biliary duct ligation and biliary drainage mice were markedly higher than those in control mice, and the protein expression of GLUT2 was not significantly altered, compared with control mice.
Answer: Bile deficiency in the intestine upregulates the expression of intestinal mucosal SGLT1 and enhances intestinal mucosal glucose absorption capacity, which contributes to the understanding of intestinal physiologic function for patients with biliary duct obstruction and external biliary drainage.

SOLUTION: Does bile deficiency induce changes in intestinal glucose absorption in mice?

PROBLEM: Context: Objective analysis of surgical skill is necessary. A novel method of assessment using simple error analysis in synthetic models is examined for construct validity.', 'Two examination protocols were devised using synthetic models. These contained either a purpose made error or were representative of good surgical practice. Protocol one contained models of skin closure and minor operations. Protocol two in addition more complex procedures. Face validity was established by the approval of senior surgeons. Junior surgeons were recruited to undertake the assessment. A p value of less than 0.05 was deemed to be significant.', 'Eighty-nine surgeons were recruited. Both protocol one and two were able to discriminate between groups at statistically significant levels.
Answer: Construct validity has been established by showing that error analysis is able to distinguish surgeons with varying levels of experience.

SOLUTION: Is the surgical error examination a novel method for objective technical knowledge assessment?

PROBLEM: Context: All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3.', 'We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production.', 'Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly.
Answer: DAAs that target NS5A rapidly inhibit intracellular assembly of genotype 1a virions. They also inhibit formation of functional replicase complexes, but have no activity against preformed replicase, thereby resulting in slow shut-off of viral RNA synthesis.

SOLUTION:
Do kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors?