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: Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear.', 'To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts.', 'Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures.', 'Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot.', 'Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways.
Answer: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.

SOLUTION: Does citrus limonoid nomilin inhibit osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways?

PROBLEM: Context: Cyclosporine causes intrarenal vasoconstriction, which may account for its nephrotoxic side effects. Plasma levels of the vasoconstrictor peptide endothelin-1 are increased after cyclosporine administration, and endothelin-1 has been shown to cause renal vasoconstriction. In this study we used in vivo microscopy to investigate the role of endothelin-1 in cyclosporine-induced vasoconstriction.', 'Hydronephrotic kidneys in decerebrate rats were suspended in an environmentally controlled tissue bath with neurovascular supply intact. Interlobular, afferent, and efferent arteriolar diameters and flow were measured by videomicroscopy and Doppler velocimetry. Cyclosporine was added to the tissue bath, and measurements were repeated for 60 minutes. In study groups endogenous endothelin-1 was blocked by infusion of either specific endothelin antiserum or an endothelin-1 receptor antagonist.', 'Cyclosporine caused constriction of the interlobular artery by 20% +/- 2% and a corresponding decrease in blood flow by 66% +/- 4%. The afferent and efferent arterioles constricted to a similar degree. This vasoconstriction was entirely prevented by infusion of either the endothelin antiserum or the receptor antagonist. The antagonist reagents alone had no effect on hemodynamic parameters or renal microvessel diameters.
Answer: The acute renal vasoconstriction induced by cyclosporine is mediated by endothelin-1. Endogenous endothelin-1 has little role in maintaining basal vascular tone.

SOLUTION: Is acute cyclosporine-induced renal vasoconstriction mediated by endothelin-1?

PROBLEM: Context: Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC.', 'All patients with UC diagnosed <17\u2005years from 1988 to 2004, and followed during >2\u2005years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models.', '158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5\u2005years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4\u2005years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1\u2005year, 45% at 5\u2005years and 52% at 10\u2005years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1\u2005year, 10% at 5\u2005years, 13% at 10\u2005years and 13% at 15\u2005years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2-E3-E4 group.
Answer: UP is frequent in paediatric-onset UC and should not be considered as a minor disease. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP, whereas the risk for use of IM was lower.

SOLUTION:
Is ulcerative proctitis a frequent location of paediatric-onset UC and not a minor disease : a population-based study?