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: PTH stimulates bone formation in Fgfr3 knockout mice through promotion of proliferation and differentiation in osteoblasts.', 'Previous studies showed that endogenous fibroblast growth factor 2 (FGF-2) is required for parathyroid hormone (PTH)-stimulated bone anabolic effects, however, the exact mechanisms by which PTH stimulate bone formation and the function of FGF receptors in mediating these actions are not fully defined. FGF receptor 3 (FGFR3) has been characterized as an important regulator of bone metabolism and is confirmed to cross-talk with PTH/PTHrP signal in cartilage and bone development.', 'Fgfr3 knockout and wild-type mice at 2-month-old and 4-month-old were intraperitoneally injected with PTH intermittently for 4 weeks and then the skeletal responses to PTH were assessed by dual energy X-ray absorptiometry (DEXA), micro-computed tomography (CT) and bone histomorphometry.', 'Intermittent PTH treatment improved bone mineral density (BMD) and femoral mechanical properties in both Fgfr3 (-/-) and wild-type mice. Histomorphometric analysis showed that bone formation and bone resorption were increased in both genotypes following PTH treatment. PTH treatment increased trabecular bone volume (BV/TV) in WT and Fgfr3-deficient mice. The anabolic response in Fgfr3-deficient and wild-type bone is characterized by an increase of both bone formation and resorption-related genes following PTH treatment. In addition, we found that Fgfr3 null osteoblasts (compared to wild-type controls) maintained normal abilities to response to PTH-stimulated increase of proliferation, differentiation, expression of osteoblastic marker genes (Cbfa1, Osteopontin and Osteocalcin), and phosphorylation of Erk1/2.
Answer: Bone anabolic effects of PTH were not impaired by the absence of FGFR3, suggesting that the FGFR3 signaling may not be required for osteoanabolic effects of PTH activities.

SOLUTION: Does fibroblast Growth Factor Receptor 3 Deficiency Impair the Osteoanabolic Action of Parathyroid Hormone on Mice?

PROBLEM: Context: Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) are controversial and mostly based on a heterologous rat Nb2 cell bioassay. Biological activity of bbPRL observed in vitro but not in vivo may be due to its high molecular weight, preventing its passage through capillary barrier. Alternatively, bbPRL bioactivity may differ depending on the prolactin (PRL) receptor (PRLR) species specificity.', 'The objective of the study was to characterize the bioactivity of bbPRL in a homologous bioassay: Ba/F-3 cells stably expressing the human PRLR.', "Chromatography-purified bbPRL from macroprolactinemic individuals (group I, n = 18) and monomeric PRL from hyperprolactinemic patients without macroprolactinemia (group II, n = 5) were tested in Nb2 and Ba/F-LLP bioassays. Both groups were followed up at the neuroendocrinology outpatients' clinic.", 'Biological activity of bbPRL presented in the two bioassays was measured.', 'In group I, no patient had hypogonadism. Mean ratio bioactivity to immunoactivity of bbPRL in the Nb2 assay was 0.69. There was no dose-response in 15 of the 18 samples tested in Ba/F-LLP assay. In group II, three patients had galactorrhea and all five had hypogonadism. Mean ratio bioactivity to immunoactivity of monomeric PRL samples was 1.35 in Nb2 and 0.91 in Ba/F-LLP assay.
Answer: Whereas both bioassays achieve similar results with respect to monomeric PRL activity, our results indicate that the activity displayed by bbPRL toward the rat receptor may be inappropriate because it is not observed in the human PRLR-mediated assay, consistent with the apparent absence of bioactivity in vivo.

SOLUTION: Does human macroprolactin display low biological activity via its homologous receptor in a new sensitive bioassay?

PROBLEM: Context: To risk-stratify patients for urinary retention after prostate brachytherapy according to a novel seed implant retention score (SIRS).', 'A total of 835 patients underwent transperineal prostate seed implant from March 1993 to January 2007; 197 patients had (125)I and 638 patients had (103)Pd brachytherapy. Four hundred ninety-four patients had supplemental external-beam radiation. The final downsized prostate volume was used for the 424 patients who had neoadjuvant hormone therapy. Retention was defined as reinsertion of a Foley catheter after the implant.', 'Retention developed in 7.4% of patients, with an average duration of 6.7 weeks. On univariate analysis, implant without supplemental external-beam radiation (10% vs. 5.6%; p = 0.02), neoadjuvant hormone therapy (9.4% vs. 5.4%; p = 0.02), baseline alpha-blocker use (12.5% vs. 6.3%; p = 0.008), and increased prostate volume (13.4% vs. 6.9% vs. 2.9%, >45 cm(3), 25-45 cm(3), <25 cm(3); p = 0.0008) were significantly correlated with increased rates of retention. On multivariate analysis, implant without supplemental external-beam radiation, neoadjuvant hormone therapy, baseline alpha-blocker use, and increased prostate volume were correlated with retention. A novel SIRS was modeled as the combined score of these factors, ranging from 0 to 5. There was a significant correlation between the SIRS and retention (p < 0.0001). The rates of retention were 0, 4%, 5.6%, 9%, 20.9%, and 36.4% for SIRS of 0 to 5, respectively.
Answer: The SIRS may identify patients who are at high risk for prolonged retention after prostate brachytherapy. A prospective validation study of the SIRS is planned.

SOLUTION:
Do seed implant retention score predicts the risk of prolonged urinary retention after prostate brachytherapy?