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: Corticosteroids are a critical component of therapy for acute lymphoblastic leukemia (ALL) but are associated with late effects, such as osteoporosis. Risk factors remain poorly defined. Because CRHR1 polymorphisms have been associated with other corticosteroid effects, our goal was to define whether CRHR1 polymorphisms predict which patients with ALL are likely to develop bone mineral deficits.', 'The mean bone mineral density z scores of 309 long-term survivors of ALL were determined by quantitative computed tomography of the trabecular lumbar spine. We analyzed whether CRHR1 genotypes, adjusted for sex, ALL treatment regimen, and weight, could predict bone density.', 'We found that three single nucleotide polymorphisms (SNPs), all in linkage disequilibrium, were associated with bone density in a sex-specific manner. Bone density was lower in males (P = .001), in nonblack patients (P < .08), in those who were not overweight (P < .001), and in those who received intensive antimetabolites and glucocorticoids (P < .001). After adjustment for these features, the G allele at the rs1876828 SNP was associated with lower z scores (P = .02) in males but tended to have the opposite association in females (P = .09).
Answer: CRHR1 polymorphisms may impact the risk of bone density deficits in patients treated with corticosteroids and antimetabolites in a sex-specific manner.

SOLUTION: Do cRHR1 polymorphisms predict bone density in survivors of acute lymphoblastic leukemia?

PROBLEM: Context: Reduced fertilization rates in women with minor endometriosis may be the result of direct effects on the ovary or to primary dysfunction within the hypothalamic-pituitary-ovarian axis. This controlled study was designed to examine the steroidogenic potential of luteinized granulosa cells in women with minor endometriosis.', 'Granulosa cells were harvested at oocyte recovery and incubated for 3 hr in increasing concentrations of luteinizing hormone (LH). The dissociation constant for added concentrations of LH was computed (as Km LH) and the results were compared between women with endometriosis and controls.', 'Women with minor endometriosis had a higher dissociation constant than women with tubal damage [Km 0.98 (0.58-9.24) versus 0.33 (0.28-0.72) ng/mL, P = 0.019], indicating reduced sensitivity to LH.
Answer: In women with endometriosis, granulosa cells were less sensitive to LH stimulation. This provides further evidence for primary ovarian dysfunction as a significant contributory cause of the associated subfertility.

SOLUTION: Are pre-ovulatory granulosa cells of infertile women with endometriosis less sensitive to luteinizing hormone?

PROBLEM: Context: Granulation tissue remodeling and myofibroblastic differentiation are critically important events during wound healing. Tobacco smoking has a detrimental effect in gingival tissue repair. However, studies evaluating the effects of cigarette smoke on these events are lacking.', 'We used gingival fibroblasts cultured within free-floating and restrained collagen gels to simulate the initial and final steps of the granulation tissue phase during tissue repair. Collagen gel contraction was stimulated with serum or transforming growth factor-1. Cigarette smoke condensate (CSC) was used to evaluate the effects of tobacco smoke on gel contraction. Protein levels of alpha-smooth muscle actin, 1 integrin, matrix metalloproteinase-3 and connective tissue growth factor were evaluated through Western blot. Prostaglandin E(2) (PGE(2)) levels were determined through ELISA. Actin organization was evaluated through confocal microscopy.', 'CSC reduced collagen gel contraction induced by serum and transforming growth factor-1 in restrained collagen gels. CSC also altered the development of actin stress fibers in fibroblasts cultured within restrained collagen gels. PGE(2) levels were strongly diminished by CSC in three-dimensional cell cultures. However, other proteins involved in granulation tissue remodeling and myofibroblastic differentiation such as alpha-smooth muscle actin, 1 integrin, matrix metalloproteinase-3 and connective tissue growth factor, were unmodified by CSC.
Answer: CSC may alter the capacity of gingival fibroblasts to remodel and contract a collagen matrix. Inhibition of PGE(2) production and alterations of actin stress fibers in these cells may impair proper tissue maturation during wound healing in smokers.

SOLUTION:
Does cigarette smoke condensate inhibit collagen gel contraction and prostaglandin E2 production in human gingival fibroblasts?