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: Critical size defects (CSDs) of bone are defined as defects that do not heal spontaneously to new bone during the lifetime of an adult individual. In contrast, immature animals are capable to heal defects of identical size. It was our hypothesis that age-related paracrine effects are relevant for this difference in regeneration.', 'The pooled supernatant of primary rat calvarial osteoblast-like cell cultures (POBC) derived from prenatal or postnatal donors was concentrated and applied into CSDs of adult recipient organisms (n = 10). In addition, the supernatant of POBC derived from prenatal donors was pooled and purified by reverse-phase chromatography. Each pre-purified fraction was tested in a proliferation indicating bioassay. Peptide fractions containing proliferative activities were re-chromatographed and re-tested in a bioassay. Finally, a proliferative activity was purified, identified by sequence analysis and applied into CSDs of adult recipients.', 'The application of POBC derived from prenatal donors resulted in osseous regeneration of a CSD in adult recipients, while the supernatant of postnatal donors had much smaller effects. The morphologic features resembled the spontaneous osseous healing of calvarial defects of the same size in immature organisms. The polypeptide "tissue inhibitor of metalloproteinases type II"(TIMP-2) was isolated from the supernatant of cultures of POBC derived from prenatal donors by measuring the induction of their proliferation. Additionally, the application of human TIMP-2 injected into calvarial CSDs of adult organisms resulted in osseous healing.
Answer: We conclude that one component responsible for the healing effect of CSDs of POBC supernatants derived from prenatal donors is TIMP-2.

SOLUTION: Is tissue inhibitor of metalloproteinases II ( TIMP-2 ) an osteoanabolic factor in vitro and in vivo?

PROBLEM: Context: Preterm delivery and sub-optimal fetal growth are associated with each other and affect both mother and infant. Our aim was to determine (i) whether there are detectable differences in DNA methylation between early and late gestation and (ii) whether changes in DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth.', 'We conducted a case-control study nested within a large prospective cohort. Gene specific methylation was measured by Methyl-Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry and 3', 'There was significantly decrease in DNA methylation in 15 of 24 genes during the 3
Answer: These data suggest that epigenetic modification is associated with an increased risk of spontaneous preterm delivery, spontaneous preterm delivery with reduced fetal growth in particular.

SOLUTION: Is spontaneous Preterm Delivery , Particularly with Reduced Fetal Growth , Associated with DNA Hypomethylation of Tumor Related Genes?

PROBLEM: Context: The protective functions of oestrogen therapy alone on cardiovascular risk parameters are well established; however, the action of progesterone on vascular parameters in an oestrogen-deprived environment is less clear.', 'To examine the effects of progesterone alone on vascular function and hormone levels in postmenopausal women.', 'In a randomized, double-blind, cross-over design study, 20 healthy postmenopausal women were tested before and after 6 weeks of treatment with micronized progesterone (100 mg/daily) and matching placebo.', 'Tests included measurement of sex hormones and gonadatropin levels, lipids and measures of surrogate markers of vascular function including, blood pressure, flow-mediated dilation of the brachial artery, systemic arterial compliance and cutaneous vascular reactivity.', 'The mean (+/- SEM) age of subjects was 56.4 +/- 2.7 years and the average body mass index at the baseline visit was 27.1 +/- 1.0 kg/m2. Progesterone levels increased as a result of progesterone treatment (0.9 +/- 0.2 to 9.5 +/- 2.3 nmol/l, P = 0.001), whereas follicle-stimulating hormone levels decreased (75.1 +/- 11.4 to 67.6 +/- 10.0, P = 0.001). Systemic arterial compliance, flow mediated dilation, cutaneous vascular reactivity, blood pressure, body mass index, plasma levels of cholesterol, lipids and oestrogen were unchanged.
Answer: We conclude that progesterone given without oestrogen does not adversely affect vascular function in postmenopausal women.

SOLUTION:
Does progesterone influence vascular function in postmenopausal women?