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: Bradykinin is a neuropeptide released after tissue damage which plays an important role in inflammatory pain. The up-regulation of the bradykinin B1 receptor in response to inflammation makes it an attractive target for drug development. Aim was to investigate if the selective B1 receptor antagonist BI113823 reduces inflammation-induced mechanical hyperalgesia and if the effect is mediated via peripheral and/or spinal B1 receptor antagonism.', "Electrophysiological recordings of peripheral afferents and spinal neurons were combined with behavioural experiments to better understand the underlying mechanisms of B1 receptor antagonism. Experiments were performed 24h after injection of complete Freund's adjuvant (CFA) or saline into the paw of Wistar rats. A gene expression analysis for the B1 receptor was performed in different tissues. BI113823 was administered orally or intrathecally to assess effects on CFA-induced hyperalgesia. Peripheral afferents of the saphenous nerve as well as spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were recorded, and mechanosensitivity was measured before and after BI113823 administration.", 'BI113823 reduced CFA-induced mechanical hyperalgesia when administered orally or intrathecally. An increased B1 receptor gene expression was found in peripheral and spinal neural tissue. BI113823 significantly reduced mechanosensitivity of peripheral afferents and spinal NS neurons, but had no effect on WDR neurons.
Answer: The selective bradykinin B1 receptor antagonist BI113823 reduces CFA-induced mechanical hyperalgesia which is mediated via antagonism of peripheral as well as spinal bradykinin B1 receptors. The selective modulation of CFA-sensitized spinal NS neurons by BI113823 could be a promising property for the treatment of inflammatory pain.

SOLUTION: Does the bradykinin B1 receptor antagonist BI113823 reverse inflammatory hyperalgesia by desensitization of peripheral and spinal neurons?

PROBLEM: Context: Chronic HIV/HCV co-infection carries increased risk of cirrhosis, hepatocellular carcinoma, and death. Due to anti-inflammatory properties, HMG co-A inhibitors (statins) may be useful adjunctive therapy to reduce liver disease progression.', 'Clinical information was extracted from the Veterans Affairs HIV and HCV Clinical Case Registries (1999 - 2010). HIV-related variables included combination anti-retroviral therapy (cART) era of diagnosis, CD4 cell count, and percent time with undetectable HIV viral load. Metabolic variables included diabetes, low-HDL, and hypertension. Statin use was measured as percent time with active prescription (time-updated throughout the follow-up period). Cox proportional hazards analysis was used to determine risk factors for cirrhosis (ICD-9 or APRI>2) overall and in groups stratified by alanine aminotransferase (ALT) level above and below 40IU/L.', 'The cohort included 5985HIV/HCV co-infected veterans. The majority was black race, and the mean age at index date was 45 years. Statin use was significantly protective of cirrhosis for patients with ALT 40IU/L; for every 30% increase in time on statin, there was a 32% decreased risk of developing cirrhosis (HR 0.68, 95% CI 0.47 -0.98). Diabetes and low-HDL were significantly associated with cirrhosis in patients with ALT > 40IU/L (HR 1.15, p<0.04 and HR 1.3, p<0.0001).
Answer: Statin drug use is beneficial in mitigating the risk of liver disease progression for HIV/HCV co-infected patients without advanced liver disease. Low-HDL and diabetes in co-infected patients with abnormal ALT have greater risk of cirrhosis development.

SOLUTION: Do statin drugs decrease progression to cirrhosis in HIV/HCV co-infected individuals?

PROBLEM: Context: Exclusion of macroprolactinaemia, a well-recognised interference, as the cause of hyperprolactinaemia is essential to avoid potential misdiagnosis and mismanagement of patients. We have derived gender-specific serum total and post-polyethylene glycol (PEG) precipitation monomeric reference ranges for the recently re-standardised Abbott Architect prolactin assay.', "Prolactin was measured in serum samples obtained from males (n=49) and females (n=52) using the current Abbott Architect immunoassay pre- and post-PEG precipitation. Gender-specific reference ranges were derived for total and monomeric (post-PEG) prolactin. Routine patients' samples (n=175) with a serum total prolactin >700 mIU/L were screened for macroprolactinaemia to assess classification compared with our previous post-PEG precipitation percentage recovery-based approach.", "Reference ranges for serum total prolactin were 58-419 mIU/L (male) and 63-561 mIU/L (female). Male and female monomeric prolactin reference ranges were 32-309 mIU/L and 39-422 mIU/L, respectively. Mean (SD) post-PEG percentage recovery of the IS 84/500 prolactin standard was 80 (2.3)%. Of 175 patients' samples screened for macroprolactinaemia, 149 had monomeric prolactin concentrations (median monomeric prolactin=1035 mIU/L; median recovery=83%) above the gender-specific reference range. Monomeric prolactin concentrations (median monomeric prolactin=162 mIU/L; median recovery=20%) in the remaining 26 were within the reference ranges. One patient classified as macroprolactin positive and another classified as macroprolactin negative would not have been identified as such using the previous recovery-based approach.
Answer: The use of post-PEG monomeric reference ranges not only identifies hyperprolactinaemia due solely to macroprolactinaemia but has the added advantage of identifying patients who have simultaneous true monomeric hyperprolactinaemia and elevated concentrations of macroprolactin.

SOLUTION:
Does reference range for serum total and monomeric prolactin for the current generation Abbott Architect assay?