Given a passage, 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.

Example Input: To describe the variability in rheumatology visits and referrals to other medical specialties of patients with spondyloarthritis (SpA) and to explore factors that may influence such variability.', 'Nation-wide cross-sectional study performed in 2009-2010. Randomly selected records of patients with a diagnosis of SpA and at least one visit to a rheumatology unit within the previous 2\xa0years were audited. The rates of rheumatology visits and of referrals to other medical specialties were estimated-total and between centres-in the study period. Multilevel regression was used to analyse factors associated with variability and to adjust for clinical and patient characteristics.', "1168 patients' records (45 centres) were reviewed, mainly ankylosing spondylitis (55.2\xa0%) and psoriatic arthritis (22.2\xa0%). The patients had incurred in 5908 visits to rheumatology clinics (rate 254 per 100 patient-years), 4307 visits to other medical specialties (19.6\xa0% were referrals from rheumatology), and 775 visits to specialised nurse clinics. An adjusted variability in frequenting rheumatology clinics of 15.7\xa0% between centres was observed. This was partially explained by the number of faculties and trainees. The adjusted intercentre variability for referrals to other specialties was 12.3\xa0%, and it was associated with urban settings, number of procedures, and existence of SpA dedicated clinics; the probability of a patient with SpA of being referred to other specialist may increase up to 25\xa0% depending on the treating centre.
Example Output: Do centre characteristics determine ambulatory care and referrals in patients with spondyloarthritis?

Example Input: Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. However, the underlying mechanisms are not fully understood. Accumulating evidence shows that the elevated vascular tone in hypertension is a consequence of the 'ion channel remodelling' that occurs during sustained high BP. The present study investigated the effects of aerobic exercise on the electrical remodelling of L-type Ca(2+) (Cav 1.2) and large-conductance Ca(2+) -activated K(+) (KCa 1.1) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHRs).", 'SHRs and normotensive (Wistar-Kyoto) rats were subjected to aerobic training or kept sedentary, and vascular mechanical and functional properties were evaluated.', 'Exercise did not affect the heart weight, but reduced the heart rate and body weight in SHR. In mesenteric arterial myocytes, exercise normalized the increased Cav 1.2 and KCa 1.1 current density in SHRs. Exercise also ameliorated the increased open probability and mean open time of the single KCa 1.1 channel in hypertension. The isometric contraction study revealed that both nifedipine (Cav 1.2 channel blocker) and NS11021 (KCa 1.1 channel activator) induced concentration-dependent vasorelaxation in MAs precontracted with noradrenaline. Exercise normalized the increased sensitivity of tissues to nifedipine and NS11021 in SHR. Furthermore, protein expression of the Cav 1.2 α1C -subunit together with the KCa 1.1 α- and β1-subunit was significantly increased in SHRs; and exercise ameliorated these molecular alterations in hypertension.
Example Output: Does chronic exercise normalize changes in Cav 1.2 and KCa 1.1 channels in mesenteric arteries from spontaneously hypertensive rats?

Example Input: Atrial natriuretic peptide (ANP) is a hormone that has both antihypertrophic and antifibrotic properties in the heart. We hypothesized that myocyte-derived ANP inhibits endothelin (ET) gene expression in fibroblasts.', 'We have investigated the mechanism(s) involved in the antiproliferative effect of ANP on cardiac fibroblasts in a cell culture model. We found that cardiac myocytes inhibited DNA synthesis in co-cultured cardiac fibroblasts as did treatment with the ET-1 antagonist BQ610. The effect of co-culture was reversed by antibody directed against ANP or the ANP receptor antagonist HS-142-1. ANP inhibited the expression of the ET-1 gene and ET-1 gene promoter activity in cultured fibroblasts. The site of the inhibition was localized to a GATA-binding site positioned between -132 and -135 upstream from the transcription start site. GATA4 expression was demonstrated in cardiac fibroblasts, GATA4 bound the ET-1 promoter both in vitro and in vivo, and siRNA-mediated knockdown of GATA4 inhibited ET-1 expression. ET-1 treatment resulted in increased levels of phospho-serine(105) GATA4 in cardiac fibroblasts and this induction was partially suppressed by co-treatment with ANP.
Example Output:
Does atrial natriuretic peptide suppress endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4-dependent mechanism?